Sickle cell disease in infancy and childhood: Routine health care maintenance and anticipatory guidance

INTRODUCTION — Children with sickle cell disease (SCD) face a wide range of health issues, and it is important that they receive appropriate anticipatory guidance and comprehensive care addressing their unique needs. This topic will review the approach to providing routine care and anticipatory guidance for children with SCD. It is intended for use both by SCD specialists and by primary care providers who are participating in the comprehensive care of children with SCD.

The guidance in this topic represents a synthesis of the standards promoted by various professional societies including the American Society of Hematology; American College of Emergency Physicians; American Academy of Pediatrics; Centers for Disease Control and Prevention; and the National Heart, Lung, and Blood Institute [1-10]. Links to these resources are provided separately. (See 'Society guideline links' below.)

Different institutions providing care to children with SCD may have different approaches to implementing the policies and patient education goals outlined below. Indeed, the categorization of common sickle cell complications may differ by program [11]. However, the basic principles are consistent.

The key elements of routine health care maintenance and anticipatory guidance for children with SCD are outlined here. Other aspects of the evaluation and management of SCD are discussed in separate topic reviews:

●Acute chest syndrome (ACS) (see "Acute chest syndrome (ACS) in sickle cell disease (adults and children)")

●Bone and joint complications (see "Acute and chronic bone complications of sickle cell disease")

●Cerebrovascular disease (see "Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease" and "Prevention of stroke (initial or recurrent) in sickle cell disease")

●Clinical manifestations (see "Overview of the clinical manifestations of sickle cell disease")

●Diagnosis (see "Diagnosis of sickle cell disorders")

●Fever (see "Evaluation and management of fever in children and adults with sickle cell disease")

●Hepatic disease (see "Hepatic manifestations of sickle cell disease")

●Kidney disease (see "Sickle cell disease effects on the kidney")

●Pain management (see "Acute vaso-occlusive pain management in sickle cell disease" and "Disease-modifying therapies to prevent pain and other complications of sickle cell disease" and "Evaluation of acute pain in sickle cell disease")

●Pregnancy (see "Sickle cell disease: Obstetric considerations")

●Prenatal testing (see "Hemoglobinopathy: Screening and counseling in the reproductive setting and fetal diagnosis")

●Prevention of infections (see "Prevention of infection in patients with impaired splenic function")

●Prognosis and summary of management (see "Overview of the management and prognosis of sickle cell disease")

●Priapism (see "Priapism and erectile dysfunction in sickle cell disease")

●Pulmonary complications (see "Overview of the pulmonary complications of sickle cell disease")

●Pulmonary hypertension (see "Pulmonary hypertension associated with sickle cell disease")

●Transfusion (see "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques" and "Transfusion in sickle cell disease: Management of complications including iron overload")

●Transition from pediatric to adult care (see "Sickle cell disease (SCD) in adolescents and young adults (AYA): Transition from pediatric to adult care")

MULTIDISCIPLINARY CARE — Children with SCD may have complications involving many different organ systems, and they often require involvement of multiple subspecialists. It is imperative to appropriately coordinate care when multiple specialists are involved [12]. In addition to the general pediatric provider and SCD specialist (typically a hematologist), examples of other referrals that may be appropriate depending on the child's specific health problems include:

●Anesthesiology – Perioperative care and pain management

●Cardiology – Pulmonary hypertension and/or cardiomyopathy

●Endocrinology – Impaired growth and/or delayed puberty

●General surgery – Cholecystectomy or splenectomy

●Nephrology – Hypertension, proteinuria, and/or nephropathy

●Neurology – Stroke, transient ischemic events, or headaches

●Orthopedics – Avascular necrosis of the femoral and humeral heads

●Otorhinolaryngology – Surgical management of obstructive sleep apnea (OSA)

●Pulmonary – Asthma or pulmonary hypertension

●Sleep medicine – Evaluation of suspected OSA

●Transfusion medicine – For facilitating exchange transfusion and mitigating alloimmunization risk

●Urology – Management of priapism

Other health care professionals whose consultation may be valuable for selected patients include:

●Social worker – To assist families in coping with the emotional burden of SCD, identifying resources for medical care, meeting requirements of care, addressing the child's educational and social needs, developing skills of parenting, and identifying options for adult care.

●Clinical care coordinator – To assist families in navigating the health care system and partner with all who are involved in a child's care, including schools, insurance companies, and community-based agencies. Some of these issues also may be addressed by a social worker.

●Psychologist – To offer individual counseling for children with mental health issues including depression, assess for school avoidance behavior, coordinate or administer neuropsychologic testing, advise on need for educational accommodations, and facilitate the transition to adult care.

●Educational diagnostician or school services – To inform parents/caregivers about available educational accommodations and help them communicate with the school about the child's needs.

NEWBORN SCREENING FOLLOW-UP — In the United States and in many other parts of the world, newborns are routinely screened for hemoglobinopathies. This offers the unparalleled opportunity to identify all children with SCD in the newborn period. Newborn screening for SCD is discussed in greater detail separately. (See "Diagnosis of sickle cell disorders", section on 'Newborn screening'.)

Infants with SCD identified through newborn screening should be promptly referred for consultation with clinicians experienced in the care of children with SCD. Depending upon local resources, the SCD clinician may be a pediatric hematologist (often within a specialized SCD center or program) or a knowledgeable general pediatric provider.

INITIAL VISIT

Timing — The timing of the first visit with an experienced SCD clinician depends upon the hemoglobin (Hb) pattern on the newborn screen. For those with an FS pattern (table 1), suggesting Hb SS or Hb S-β⁰ thalassemia, the infant should be seen by the SCD expert by six to eight weeks. It is important to begin prophylactic penicillin early in these patients since splenic function begins to decline by the age of two to three months. For infants with other newborn screen patterns who generally do not display early clinical symptoms, the first SCD clinical visit may be delayed until 12 to 16 weeks of age, depending on local resources. (See "Diagnosis of sickle cell disorders", section on 'Hemoglobin patterns'.)

The first visit is critical to confirm the diagnosis, introduce anticipatory guidance, start penicillin prophylaxis, review and update vaccinations, alleviate parental/caregiver concerns, dispel misconceptions, and discuss implications for the parental genotypes (for their own health care and for future children). Typically, the first visit is with a hematologist; however, in settings with limited access to specialty care, it may be with a pediatrician who is well informed and experienced in caring for children with SCD.

Laboratory testing

●Confirmation of exact diagnosis – The confirmation of an exact diagnosis will depend on the testing provided by the newborn screening program. At least two separate blood tests, including the immediate newborn sample, should be used to confirm the initial findings. Confirmatory testing may be provided by subsequent Hb analysis using a different technique than the one used for newborn screening. Examples of methods used in newborn screening include electrophoresis, high-performance liquid chromatography, and DNA-based tests. These tests confirm the identity of the variant Hb(s) present and thus the specific type of SCD. The approach is described in detail separately. (See "Diagnosis of sickle cell disorders".)

●Complete blood count and reticulocyte count – A complete blood count with reticulocyte count should be performed at the first visit and at each subsequent visit to establish baseline values for the individual patient. The results should be interpreted in view of the physiologic decline of Hb in infants.

Medication

Prophylactic penicillin — Beginning by two months of age and continuing until at least age five years, all patients with Hb SS and Hb S-β⁰ thalassemia should receive prophylactic penicillin V potassium [13].

The dose depends on the age of the child [13]:

●Age 2 months to <3 years – 125 mg orally twice daily

●Age ≥3 years – 250 mg orally twice a day

The oral solution of penicillin must be stored in a refrigerator and refilled every 14 days, which can be inconvenient and costly for the family. Therefore, some clinicians and caregivers prefer to use penicillin V potassium 250 mg tablets (one-half a tablet in children <3 years), which can be crushed and mixed in a small amount of formula or water. However, there are few published data to support this practice [14]. Erythromycin is the alternative for penicillin-allergic patients.

The evidence supporting the efficacy of prophylactic penicillin in children with SCD is discussed in a separate topic review. (See "Overview of the management and prognosis of sickle cell disease", section on 'Prophylactic penicillin'.)

Children with other sickle cell syndromes such as Hb SC disease and Hb S-β⁺ thalassemia are not routinely prescribed prophylactic penicillin, due to the lower incidence and/or later onset of functional asplenia. This issue is discussed separately. (See "Overview of the management and prognosis of sickle cell disease", section on 'Hb SC disease and sickle cell-beta thalassemia'.)

In addition to prophylactic penicillin, caregivers should understand the fever management plan and should be counselled about the importance of following the recommended immunization schedule for immunocompromised children, as discussed separately. (See 'Fever plan' below and "Prevention of infection in patients with impaired splenic function", section on 'Vaccinations'.)

Folic acid — Folic acid (400 micrograms to 1 mg daily) is often given to children with Hb SS and Hb S-β⁰ thalassemia (and other hemolytic anemias). However, clinicians may reasonably omit folic acid for patients in resource-abundant settings who have sufficient dietary intake, especially in settings where grains and cereals are routinely supplemented. Formula-fed infants in particular receive adequate folic acid in their diet. (See "Causes and pathophysiology of vitamin B12 and folate deficiencies", section on 'Inadequate dietary intake'.)

Hydroxyurea and other disease-modifying therapies — Hydroxyurea is the principal disease-modifying therapy for SCD. When given regularly at appropriate doses, it decreases the frequency and severity of vaso-occlusive complications (eg, dactylitis, painful episodes, acute chest syndrome [ACS]) and it may reduce the risk of organ damage in individuals with Hb SS and Hb S-β⁰ thalassemia. Its efficacy in other SCD variants (eg, Hb SC and Hb S-β⁺ thalassemia) is less certain, but it may offer the same benefits.

We introduce the concept of starting hydroxyurea during each visit in infancy, including written materials to ensure that families are well informed about the benefits and risks of this therapy. We generally offer hydroxyurea beginning at nine months of age regardless of prior symptoms. This approach is consistent with the National Heart, Lung, and Blood Institute consensus guidelines [1].

Details regarding the use of hydroxyurea in patients with SCD, including dosing information, side effects, monitoring, and evidence of efficacy, are provided in a separate topic review. (See "Hydroxyurea use in sickle cell disease".)

Options for patients who cannot take hydroxyurea or who have continued symptoms despite optimally dosed hydroxyurea include L-glutamine, crizanlizumab, and voxelotor. These are discussed separately. (See "Disease-modifying therapies to prevent pain and other complications of sickle cell disease", section on 'Options if hydroxyurea is not tolerated or ineffective in individuals with Hb SS or Hb S-Beta(0)-thalassemia'.)

Education — The child's parents or caregivers should be educated about acute and chronic complications of SCD (table 2). This is a cornerstone of effective medical care and is discussed in detail in the sections below. (See 'Anticipatory guidance' below.)

Most aspects of anticipatory guidance should be introduced at the initial visit and then reviewed during each follow-up visit to reinforce the information and ensure understanding. Two issues that are particularly important at the initial visit are instructions for managing fevers and for regularly palpating the spleen. This is because febrile illnesses and splenic sequestration are problems that tend to arise in early infancy. (See 'Fever plan' below and 'Splenic sequestration' below.)

In addition, the following information should be provided at the first visit:

●Risk in subsequent pregnancies – SCD is an autosomal recessive condition. The chance of having another child with SCD depends on the genotypes of the parents. If both parents are heterozygous (with sickle cell trait or other beta globin variant), the risk of having another affected child is 25 percent. If either parent is homozygous for a beta globin variant, the risk is 50 percent and, if both are homozygous, all children will be affected. If either parent has a subsequent pregnancy with another partner, the risk of recurrence will depend on that person's hemoglobinopathy status. Each parent should be encouraged to share the information about their status with any future partners to allow for informed decision-making before another child is conceived. This issue is discussed in greater detail separately. (See "Sickle cell trait", section on 'Reproductive issues' and "Hemoglobinopathy: Screening and counseling in the reproductive setting and fetal diagnosis".)

●How to contact the sickle cell specialist – Expert advice should be available to the caregivers of a child with SCD whenever needed. Contact information should be provided in writing to the family, for use when calling with follow-up questions or with new problems or when a complication such as fever or splenic enlargement develops that requires urgent medical evaluation. At a minimum, contact information should be provided to allow general practitioners and emergency clinicians who are seeing the patient for an acute problem to consult the specialist at any time.

FOLLOW-UP VISITS — The interval of follow-up with the SCD clinician or team is individualized based upon SCD type, family needs, other medical conditions, distance from expert care, and insurance requirements. We suggest a minimum of a 20- to 30-minute visit at the intervals indicated in the sections below. The visit should be dedicated to anticipatory guidance concerning issues specific to SCD and for verification of disease-specific immunization needs. This series of visits should be in addition to those needed for general pediatric primary care.

If vaccines are provided outside of the specialized SCD program, the SCD specialist should advise the family and primary care provider about disease-specific vaccine requirements, which are outlined below. (See 'Additional age-specific care' below.)

Routine monitoring at all visits — The following assessments should be performed at all visits to the SCD clinician:

●Height, weight, and head circumference should be measured, plotted on growth curves, and compared with prior values. Children with SCD often have some decrement of growth between 6 and 24 months of age, corresponding to the decline in hemoglobin (Hb) associated with increased beta chain synthesis. However, the subsequent rate of growth should be normal. Growth velocity data are particularly important in assessment of pubertal delays or of short stature and in related treatment decisions [15,16]. (See "Approach to the patient with delayed puberty" and "Diagnostic approach to children and adolescents with short stature".)

●Vital signs, including blood pressure, should be measured at each visit [17]. Early recognition and management of hypertension has become a priority because of increased awareness of the high mortality in adults with SCD and end-stage kidney disease [1,18]. Blood pressure should be assessed during well visits when the child is at rest. Baseline blood pressure in children with SCD is generally lower than age-matched controls, and an increase in blood pressure within the normal range may actually represent hypertension for that individual. Hypertension noted only during painful episodes is most often attributable to pain. Normative data and definitions of hypertension in children are summarized in the tables (table 3 and table 4 and table 5). The evaluation and diagnosis of hypertension in children are discussed separately. (See "Sickle cell disease effects on the kidney", section on 'Blood pressure abnormalities' and "Evaluation of hypertension in children and adolescents".)

●Room air peripheral oxygen saturation (SpO₂) should be recorded at least annually, using a pulse oximeter. SpO₂ values are generally lower in children with SCD compared with the general population. Therefore, it is important to have serial measurements of each child's baseline value when healthy to be used for comparison when the child presents with an acute medical issue, such as a painful episode or acute chest syndrome (ACS).

●Complete blood count and reticulocyte count should be done at each SCD-specific visit (at a minimum, annually, and more frequently for those receiving hydroxyurea), and a copy of the results should be given to the family. The family should be asked to bring this information for comparison if the child presents to an outside institution for an acute problem (eg, splenic sequestration or an acute pain episode).

●Extended red blood cell antigen profile (by genotype or serology), at least for the Rh (CcDEe) and Kell antigens, should be considered in all patients with Hb SS or Hb S-β⁰ thalassemia at a clinic visit in early childhood in anticipation of a high likelihood of transfusion during childhood. Alternatively, some institutions offer strategies to perform this typing rapidly when transfusion is needed [19]. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'RBC antigen matching' and "Red blood cell antigens and antibodies".)

Additional age-specific care

Age zero to two years

●Intervals for visits

•Hb SS and Hb S-β⁰ thalassemia – Every three to four months

•Hb SC and Hb S-β⁺ thalassemia – Every four to six months (more frequently if experiencing frequent symptoms)

●Immunizations – Infants and children should receive all routine childhood vaccinations, as discussed separately. (See "Standard immunizations for children and adolescents: Overview", section on 'Routine schedule'.)

Particular attention should be paid to the following:

•Administer the pneumococcal conjugate vaccine (PCV) series (either 15- or 20-valent PCV can be given [PCV20 is preferred, if available]) and Haemophilus influenzae type b (Hib) series (figure 1) [20]. These immunizations are part of the routine vaccination schedule for all children but are particularly important for children with SCD due to increased risk for severe infection caused by functional asplenia. (See "Standard immunizations for children and adolescents: Overview", section on 'Routine schedule' and "Prevention of infection in patients with impaired splenic function", section on 'Vaccinations'.)

•For infants ≥6 months old, administer inactivated influenza vaccine annually. (See "Seasonal influenza in children: Prevention with vaccines".)

•Coronavirus disease 2019 (COVID-19) vaccination once ≥6 months old. (See "COVID-19: Vaccines", section on 'Children aged six months to four years'.)

•Meningococcal vaccination is important in individuals with SCD. Children with Hb SS and Hb S-β⁰ thalassemia should receive meningococcal vaccination according to recommendations for asplenic individuals, as summarized in the table (table 6A) and discussed in detail separately. (See "Meningococcal vaccination in children and adults", section on 'Immunization of persons at increased risk'.)

•Respiratory syncytial virus (RSV) prophylaxis for eligible infants, as discussed separately. (See "Respiratory syncytial virus infection: Prevention in infants and children".)

●Medications:

•Penicillin – Penicillin prophylaxis is indicated for children with Hb SS and Hb S-β⁰ thalassemia. Children with Hb SC and Hb S-β⁺ thalassemia are not routinely prescribed prophylactic penicillin, due to the lower incidence of functional asplenia and/or onset at a later age. When indicated, penicillin prophylaxis should be started by two to three months of age. (See 'Prophylactic penicillin' above and "Overview of the management and prognosis of sickle cell disease", section on 'Prophylactic penicillin'.)

•Hydroxyurea – Hydroxyurea is the principal disease-modifying therapy for SCD. It has been demonstrated to reduce vaso-occlusive complications (pain, ACS) and may improve survival. Hydroxyurea should be offered to all patients with Hb SS or Hb S-β⁰ thalassemia beginning at the age of nine months. Dosing information, side effects, monitoring, and evidence of efficacy are provided in a separate topic review. (See "Hydroxyurea use in sickle cell disease".)

Other options are available for those who cannot take hydroxyurea or who have continued symptoms despite optimally dosed hydroxyurea, as discussed separately. (See "Disease-modifying therapies to prevent pain and other complications of sickle cell disease", section on 'Options if hydroxyurea is not tolerated or ineffective in individuals with Hb SS or Hb S-Beta(0)-thalassemia'.)

●Anticipatory guidance – Highlight issues of recognition and management of pain episodes, fever plan, spleen palpation, stroke, and ACS. (See 'Anticipatory guidance' below.)

Age two to five years

●Intervals for visits

•Hb SS and Hb S-β⁰ thalassemia – Every three to four months

•Hb SC and Hb S-β⁺ thalassemia – Every 6 to 12 months

●Immunizations – Children with SCD should receive all routine childhood vaccinations, as discussed separately. (See "Standard immunizations for children and adolescents: Overview", section on 'Routine schedule'.)

Particular attention should be paid to the following:

•Pneumococcal vaccine – If the child has not completed the primary PCV series including at least one dose of PCV20, additional pneumococcal vaccination should be provided at this age as summarized in the figure (algorithm 1A) and discussed in detail separately. (See "Pneumococcal vaccination in children", section on 'Immunization of high-risk children and adolescents'.)

•Administer inactivated influenza vaccine annually [21]. (See "Seasonal influenza in children: Prevention with vaccines".)

•COVID-19 vaccination as appropriate. (See "COVID-19: Vaccines", section on 'Children aged six months to four years'.)

•Meningococcal vaccination should be provided if the child did not already receive the series (table 6B). The efficacy of the meningococcal vaccines in asplenic children has not been clearly established, but they are recommended for this group because of the increased risk for meningococcal infections. Other details regarding meningococcal vaccination are discussed in greater detail separately. (See "Meningococcal vaccination in children and adults".)

●Medications:

•Penicillin – For children receiving penicillin prophylaxis, the dose should be increased to 250 mg twice a day once the child turns three years old [13]. For children with SCD who completed the primary PCV series with PCV15 or PCV20 in infancy, the optimal duration of penicillin prophylaxis is uncertain. We generally continue penicillin prophylaxis until at least five years of age since the risk of invasive pneumococcal disease is highest in this age group. There are no data to suggest that it is safe to stop penicillin at an earlier age if the child has received PCV20. In a study conducted in the PCV13 era, pneumococcus remained a major cause of invasive bacterial illness in children with SCD, with approximately 65 percent of cases occurring in children <5 years [22]. Penicillin prophylaxis is discussed in greater detail separately. (See "Overview of the management and prognosis of sickle cell disease", section on 'Prophylactic penicillin'.)

•Hydroxyurea – If not previously prescribed, hydroxyurea should be offered to all patients with Hb SS or Hb S-β⁰ thalassemia regardless of severity of disease. Follow-up visits for children taking hydroxyurea should include assessment of its tolerability, adherence, routine laboratory monitoring, and dose adjustment as necessary. Details regarding the use of hydroxyurea in patients with SCD, including dosing and titration, side effects, monitoring, and evidence for efficacy, are provided in a separate topic review. (See "Hydroxyurea use in sickle cell disease".)

●Screening and management of comorbidities – Our approach to screening for associated conditions and comorbidities in children with SCD is summarized in the table (table 7). Additional details on evaluation and management of these conditions are provided in separate topic reviews:

•Asthma/reactive airways disease (see "Overview of the pulmonary complications of sickle cell disease", section on 'Asthma')

•Dactylitis or pain episodes (see "Acute vaso-occlusive pain management in sickle cell disease")

•Growth failure (see "Overview of the clinical manifestations of sickle cell disease", section on 'Growth and development' and "Diagnostic approach to children and adolescents with short stature")

•Hypertension (see "Evaluation of hypertension in children and adolescents")

•Nephropathy (see "Sickle cell disease effects on the kidney")

•Obstructive sleep apnea (OSA) (see "Overview of the pulmonary complications of sickle cell disease", section on 'Sleep-disordered breathing')

•Priapism (see "Priapism and erectile dysfunction in sickle cell disease")

•Stroke (see "Prevention of stroke (initial or recurrent) in sickle cell disease")

●Anticipatory guidance – Important issues to discuss include (see 'Anticipatory guidance' below):

•Fever plan (see 'Fever plan' below)

•Spleen palpation (see 'Splenic sequestration' below)

•Home pain management (see 'Painful episodes' below)

•Stroke (see 'Stroke' below)

•Priapism (in males) (see 'Priapism' below)

•ACS (see 'Acute chest syndrome' below)

In addition, clinicians should provide anticipatory guidance about nocturnal enuresis at this age. Most children become continent day and night at some time between the age of two to five years. Children with SCD are somewhat less likely to be continent at night compared with the general pediatric population due to decreased urinary concentration related to early sickle nephropathy. Education about behavioral modification to address this issue should be offered to caregivers. Management of nocturnal enuresis is discussed in greater detail separately. (See "Nocturnal enuresis in children: Management".)

Age five years to adolescence

●Intervals for visits

•Hb SS and Hb S-β⁰ thalassemia – Every six months

•Hb SC and Hb S-β⁺ thalassemia – Every 8 to 12 months

●Immunizations – Children and adolescents with SCD should receive all routine childhood vaccinations, as discussed separately. (See "Standard immunizations for children and adolescents: Overview", section on 'Routine schedule'.)

Particular attention should be paid to the following:

•Pneumococcal vaccine – Additional pneumococcal vaccination may be required at this age if the child has not completed the primary or catch-up PCV series including at least one dose of PCV20 (algorithm 1B). Additional details are provided separately. (See "Pneumococcal vaccination in children", section on 'Immunization of high-risk children and adolescents'.)

•Administer the inactivated influenza vaccine annually. (See "Seasonal influenza in children: Prevention with vaccines".)

•COVID-19 vaccination as appropriate. (See "COVID-19: Vaccines", section on 'Children aged 5 to 11 years'.)

•If not already done, meningococcal vaccination should be administered. A single booster dose is advised every five years thereafter (table 6B). Children ≥10 years of age should receive the serogroup B meningococcal vaccine [23]. (See "Meningococcal vaccination in children and adults", section on 'Immunization of persons at increased risk'.)

•Children who were not previously immunized against Hib should receive one dose of the Hib vaccine [21]. (See "Prevention of Haemophilus influenzae type b infection".)

●Hydroxyurea – Hydroxyurea is the principal disease-modifying therapy for SCD and is recommended for children with SCD beginning at the age of nine months. Follow-up visits for children taking hydroxyurea should include assessment of its tolerability, adherence, routine laboratory monitoring, and dose adjustment as necessary. Dosing and titration, side effects, monitoring, and evidence for efficacy are provided in a separate topic review. (See "Hydroxyurea use in sickle cell disease".)

●Screening and management of comorbidities – Our approach to screening for associated conditions and comorbidities in children with SCD is summarized in the table (table 7). Additional details on evaluation and management of these conditions are provided in separate topic reviews:

•Asthma/reactive airways disease (see "Overview of the pulmonary complications of sickle cell disease", section on 'Asthma')

•Depressive disorders (see "Pediatric unipolar depression: Epidemiology, clinical features, assessment, and diagnosis")

•Growth failure and delayed puberty (see "Diagnostic approach to children and adolescents with short stature" and "Approach to the patient with delayed puberty")

•Hypertension (see "Evaluation of hypertension in children and adolescents")

•Nephropathy (see "Sickle cell disease effects on the kidney")

•OSA (see "Overview of the pulmonary complications of sickle cell disease", section on 'Sleep-disordered breathing')

•Pain episodes (see "Acute vaso-occlusive pain management in sickle cell disease")

•Priapism (see "Priapism and erectile dysfunction in sickle cell disease")

•Pulmonary hypertension (See "Pulmonary hypertension associated with sickle cell disease".)

•Retinopathy (see "Overview of the clinical manifestations of sickle cell disease", section on 'Retinopathy')

•Stroke (see "Prevention of stroke (initial or recurrent) in sickle cell disease")

●Education – Children with SCD face specific challenges in the educational setting. The following areas of concern should be reviewed:

•Ensure that the child is sent to school every day possible and that the school is prepared to administer pain medications, if needed, to help the child stay in the classroom as much as possible.

•At every visit, the child's level of educational achievement should be reviewed. Poor educational performance, particularly if there is a marked change from the child's previous attainment, may be a sign of "silent" cerebral infarcts and should prompt investigation with a brain magnetic resonance imaging/angiography. Neuropsychologic testing (if available) and educational screening should also be obtained. (See "Clinical diagnosis of stroke subtypes", section on 'Silent brain infarcts'.)

•Parents/caregivers should be advised of the federal legislative mandate in the United States regarding educational accommodation for children with special health care needs such as SCD and should be assisted in obtaining services required to support their child's education. Mechanisms for accommodation include special education and other health-impaired 504 programs. (See "Children and youth with special health care needs", section on 'School-based services'.)

●Anticipatory guidance – In this age group, there is a gradual shift towards directing anticipatory guidance to the patient rather than (or in addition to) the caregivers, as appropriate for the child's age and developmental ability. Fostering autonomy and behavioral skills at this age helps prepare the child for transition to adult care later on. Important issues to discuss include pain recognition and management, ACS, asthma control (if relevant), snoring, nocturnal enuresis, priapism in males, growth, and development, focusing on early pubertal changes. Providers should also review the fever plan, risk of stroke, and spleen palpation (if appropriate). In patients with Hb SC disease, splenic sequestration most commonly occurs after age five, whereas sequestration is uncommon after age five in patients with Hb SS and Hb S-β⁰ thalassemia since the spleen typically becomes fibrotic from repeated splenic infarct by this age. (See 'Anticipatory guidance' below.)

Older adolescents

●Intervals for visits

•Hb SS and Hb S-β⁰ thalassemia – Every six months

•Hb SC and Hb S-β⁺ thalassemia – Every 8 to 12 months

●Immunizations

•Verify that the entire pneumococcal vaccine series is complete, including at least one dose of PCV20 or two doses of PPSV23. If there is no documentation of any PCV or if doses were missed, the adolescent should receive catch-up immunization with one dose of PCV (ideally with PCV20) before age 18 years, as summarized in the figure (algorithm 1B) and discussed in detail separately. (See "Pneumococcal vaccination in children", section on 'Immunization of high-risk children and adolescents'.)

•Verify that the meningococcal vaccine series (table 6B) has been administered. (See "Meningococcal vaccination in children and adults", section on 'Immunization of persons at increased risk'.)

•Administer the inactivated influenza vaccine annually. (See "Seasonal influenza in children: Prevention with vaccines".)

•COVID-19 vaccination as appropriate. (See "COVID-19: Vaccines".)

●Screening and management of comorbidities – Our approach to screening for associated conditions and comorbidities in children with SCD is summarized in the table (table 7). Additional details on evaluation and management of these conditions are provided in separate topic reviews:

•Asthma/reactive airways disease (see "Overview of the pulmonary complications of sickle cell disease", section on 'Asthma')

•Depressive disorders (see "Pediatric unipolar depression: Epidemiology, clinical features, assessment, and diagnosis")

•Growth failure and delayed puberty (see "Diagnostic approach to children and adolescents with short stature" and "Approach to the patient with delayed puberty")

•Hypertension (see "Evaluation of hypertension in children and adolescents")

•Nephropathy (See "Sickle cell disease effects on the kidney".)

•OSA (see "Overview of the pulmonary complications of sickle cell disease", section on 'Sleep-disordered breathing')

•Pain episodes (see "Acute vaso-occlusive pain management in sickle cell disease")

•Priapism (see "Priapism and erectile dysfunction in sickle cell disease")

•Pulmonary hypertension (see "Pulmonary hypertension associated with sickle cell disease")

•Retinopathy (see "Overview of the clinical manifestations of sickle cell disease", section on 'Retinopathy')

•Stroke (see "Prevention of stroke (initial or recurrent) in sickle cell disease")

●Reproductive issues – Reproductive issues should be discussed with female and male adolescents who are sexually active. Key issues include:

•Routine counselling regarding contraception and prevention of sexually transmitted infections (see "Sickle cell disease: Obstetric considerations", section on 'Contraception' and "Contraception: Issues specific to adolescents" and "Prevention of sexually transmitted infections")

•Risks associated with pregnancy (see "Sickle cell disease: Obstetric considerations")

•Inheritance pattern and genetic risk of SCD

●Anticipatory guidance – The provider should revisit medical issues that require monitoring and should follow up to ensure that the patient clearly understands risks and goals. Highlight issues of pain, ACS, asthma control (if relevant), priapism in males, and educational/transition plan. Review fever plan, spleen palpation (for patients with Hb SC disease), and the patient's understanding of treatment options. (See 'Anticipatory guidance' below.)

●Transition planning – The transition period from pediatric to adult care for youth with SCD is especially important as they develop the knowledge, skills, and motivation to actively participate in their health care. The stakes for health and even survival are high for individuals with SCD, who often experience an increase in the use of health care resources as well as a sharp increase in mortality during the young adult years. Transition is a multidimensional process that must occur in stages that include providing information about the process, assessing readiness, coordinating communication between pediatric and adult providers, completing age-appropriate medical assessments and interventions, preparing a medical summary and an action plan for pain control and prevention, and introducing the adult provider. The general approach and the core elements of health care transition are summarized in the tables (table 8 and table 9). Transition from pediatric to adult care is discussed in greater detail separately. (See "Sickle cell disease (SCD) in adolescents and young adults (AYA): Transition from pediatric to adult care".)

Care plans — Many providers use a roadmap or outline of care that is signed off at each visit or when a milestone is reached. These care plans help ensure that appropriate education and screening have occurred. Care plans can be integrated into the medical record and may include order sets prompting the clinician to obtain screening tests or provide immunizations and other interventions at appropriate intervals in accordance with the available guidelines.

Care plans may address specific aspects of care, including:

●Chronic transfusion (see "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Prophylactic (regularly scheduled) transfusion')

●Perioperative care (see "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Prophylactic preoperative transfusion')

●Pain management (see "Acute vaso-occlusive pain management in sickle cell disease")

●Sports participation and physical education

●Transition from pediatric to adult care (see "Sickle cell disease (SCD) in adolescents and young adults (AYA): Transition from pediatric to adult care")

ANTICIPATORY GUIDANCE — Beginning with the first visit, each of the following issues should be introduced to the family. They are then reviewed and reinforced at each subsequent visit. Disease complications requiring urgent medical attention, particularly fever and splenic sequestration, should be reviewed in detail at the initial visit; detailed discussion of other complications may be delayed until later in the first year to avoid overwhelming parents and caregivers at the first visit.

When to seek care — It is particularly important that the caregivers have a clear understanding of symptoms that require urgent evaluation (table 2) and that they have an action plan. Contact information for the SCD specialist should be provided to the family, and they should have a plan for where they will bring the child if an urgent medical issue arises.

Fever plan — All caregivers should be educated that a fever requires urgent medical attention, even if the fever immediately comes down with or without antipyretics.

The threshold used to trigger evaluation in children with SCD varies from center to center; the optimal approach remains uncertain. In the United States, guidelines from the National Heart, Lung, and Blood Institute suggest using a temperature cutoff of ≥38.5°C (equivalent to approximately ≥101.3°F) to trigger evaluation [1]. However, many SCD experts use a lower cutoff, such as ≥38°C (≥100.4°F) or ≥38.3°C (≥100.9°F) [1,24].

Patients with fever should be seen as soon as possible after fever onset, at least within four hours. A specific plan should be made for where the family should bring the child with SCD when they develop a fever. Options include the primary care clinician's office, a local emergency department (ED), or a tertiary pediatric hospital ED or clinic. The evaluation includes, at a minimum, a complete blood count, blood culture, and empiric dose of parenteral antibiotic active against Streptococcus pneumoniae. Management of fever in SCD is discussed in greater detail separately. (See "Evaluation and management of fever in children and adults with sickle cell disease".)

Splenic sequestration — The family should be educated about the risk of splenic sequestration, which is heralded by splenic enlargement and an associated decline in hemoglobin (Hb) and sometimes platelet counts; this may lead acutely to severe, life-threatening anemia. Caregivers should be taught how to palpate the child's spleen and instructed to check it at least daily and more often if the child is ill. If the spleen feels enlarged, the child should be evaluated by a clinician to confirm the finding and obtain a blood count to assess if transfusion is required.

In patients with Hb SS or Hb S-β⁰ thalassemia, the risk for acute splenic sequestration crisis is highest during infancy and early childhood (up to age three years). Individuals with Hb SC also develop splenomegaly and splenic sequestration, but, typically, this occurs at an older age (school age to adulthood) and usually is not an acute clinical problem, because of the higher baseline Hb in Hb SC disease. Eventually, because of infarction, this process may lead to splenic hypofunction and to functional asplenia, placing the child at risk for overwhelming infection with encapsulated organisms. (See "Overview of the clinical manifestations of sickle cell disease", section on 'Splenic sequestration crisis' and "Prevention of infection in patients with impaired splenic function".)

Painful episodes — The parents or caregivers should be educated about management of painful episodes before the infant is four to five months old. Pain is a hallmark in all forms of SCD and is one of the most stressful and feared complications of the disease. Discussions should emphasize that pain should be recognized and treated promptly, and this point should be reiterated at subsequent visits.

The sections below highlight some of the key elements to discuss when providing anticipatory guidance to families and caregivers. A more detailed discussion of the prevention, evaluation, and management of pain in patients with SCD is provided in separate topic reviews. (See "Disease-modifying therapies to prevent pain and other complications of sickle cell disease" and "Evaluation of acute pain in sickle cell disease" and "Acute vaso-occlusive pain management in sickle cell disease".)

●Avoidance of triggers for pain

•Avoid cold temperatures – Cold causes vasoconstriction, which may precipitate or increase pain. In particular, applying ice when the child is experiencing a painful episode should be avoided because it may worsen pain. If the child is exposed to cold temperatures without protection (eg, after swimming), they should be encouraged to take a warm shower or bath and massage or rub any cold areas, as tolerated.

•Avoid dehydration – At the first sign of pain, oral fluid intake should be increased to twice maintenance volumes. The clinician should calculate this volume and communicate the target hourly volume to the family in advance of the painful event.

•Ensure adequate rest.

•Reduce stress – Social stressors should be explored at all routine visits starting in early childhood. If concerns arise, appropriate psychosocial counselling referrals should be offered. Common sources of stress in young children include school, family issues, peer relationships, and other aspects of their living conditions. Stress may cause the child to be less able to engage in appropriate self-care behaviors and may amplify the child's experience of pain.

●Recognition of pain

•Early symptoms of a painful episode in a young child often include decreased activity (or lying quietly). Symmetric or asymmetric swelling may develop in the dorsum of the hands or feet (dactylitis or hand-foot syndrome). The pain may or may not be accompanied by crying.

•School-aged children in the early stages of a painful episode either may be uninterested in usual activities or may try to ignore the pain. If the pain is not recognized and treated, it may progress to overwhelming pain, which is difficult to control. Therefore, the child should be encouraged to tell a trusted adult when they feel pain. The adult should be aware of the need for early treatment and should be educated about the different modalities available to treat pain.

•Older children and adolescents experience pain in many different ways. During office visits, the child should be engaged in discussing how to avoid triggers for their pain, how they can manage their pain at home, and how to communicate their pain to medical professionals.

●Management of pain – Details of pain management in children with SCD are beyond the scope of this topic review. The general approach is summarized in the table and discussed in greater detail in a separate topic review (table 10). (See "Acute vaso-occlusive pain management in sickle cell disease".)

Key points to discuss with caregivers at scheduled visits are:

•Nonpharmacologic measures should be used in addition to pharmacologic treatments of pain. These include distraction, reading or being read to, soft music, or other activities to induce relaxation.

•Mild pain in young children may be managed with an oral nonsteroidal antiinflammatory drug (NSAID) such as ibuprofen (10 mg/kg per dose every four to six hours; maximum 40 mg/kg per day) as needed. Caregivers should be instructed to encourage increased oral fluid intake when using NSAIDs to minimize potential kidney toxicity. (See "NSAIDs: Acute kidney injury".)

•For moderate pain, oral opioids can be given every four to six hours, depending on the agent used, alternating with an NSAID, such that one or the other medication is given every few hours. (See "Acute vaso-occlusive pain management in sickle cell disease", section on 'Management at home'.)

Medications and doses should be discussed at scheduled visits in advance of need. The family should be advised to obtain over-the-counter NSAIDs and/or given prescriptions for other medications to have at home to be used for treatment of subsequent painful events. The prescriptions should provide sufficient medication for three to four days of continuous oral outpatient pain management without refills.

•The patient and caregivers should be informed of the common side effects of opioids (eg, constipation, pruritus, nausea), and the clinician should develop a plan for management.

•If the home measures described above do not relieve the pain enough to allow the child to rest after 24 hours of scheduled home management or if pain continues to escalate, the child should present for urgent medical evaluation and possible inpatient admission.

•When the child is well (after the acute painful episode has resolved), discuss adding or adjusting disease-modifying therapies such as hydroxyurea or oral glutamine to reduce the likelihood of future painful events. (See "Disease-modifying therapies to prevent pain and other complications of sickle cell disease".)

Acute chest syndrome — Caregivers should be educated about acute chest syndrome (ACS) before the infant is six to nine months old. They should be warned that ACS is a unique complication of SCD that resembles pneumonia in an otherwise healthy child. ACS can progress quickly and can be life-threatening. It generally requires inpatient management and parenteral antibiotics [25].

Key points to communicate to the family include:

●If the child develops shortness of breath, chest pain that is not typical for them, or trouble breathing, the family should urgently seek care in an ED.

●Asthma is both a promoter and consequence of ACS episodes [26-29]. Therefore, it is essential to promptly recognize and treat asthma symptoms, including diligent use of asthma controller medications if appropriate [26,30,31]. Children with multiple ACS episodes should be referred to a pediatric pulmonologist for evaluation of undetected or undertreated asthma. (See 'Asthma' below and "Asthma in children younger than 12 years: Management of persistent asthma with controller therapies".)

●Exposure to environmental tobacco smoke increases risks for asthma and ACS. All household members who smoke should be strongly encouraged to quit and should be guided to smoking cessation resources. (See "Overview of smoking cessation management in adults".)

●If hydroxyurea has not been initiated, it should be discussed once the child has recovered from the ACS episode. (See 'Hydroxyurea and other disease-modifying therapies' above and "Hydroxyurea use in sickle cell disease".)

A detailed discussion of ACS is presented in a separate topic review. (See "Acute chest syndrome (ACS) in sickle cell disease (adults and children)".)

Asthma — Asthma is a common comorbidity in patients with SCD and is associated with increased risk of ACS [26-29]. Caregivers should be instructed to alert the clinician if the child has signs or symptoms suggestive of asthma (eg, wheezing or frequent respiratory illnesses) or if there is a family history of asthma [32]. Children with SCD who are diagnosed with asthma should be counselled about the importance of adhering to prescribed controller therapy. Management of asthma is discussed in detail separately. (See "Asthma in children younger than 12 years: Management of persistent asthma with controller therapies".)

Stroke — For infants with Hb SS or Hb S-β⁰ thalassemia, the parents or caregivers should be educated about stroke risk before the infant is nine months old [33].

Key points to communicate to the family include:

●Approximately 1 in 10 children with Hb SS experiences ischemic stroke by age 18. Warning signs of stroke include severe headache; difficulty speaking; and not moving a side of the face, arm, or leg, in the absence of pain. These stroke symptoms may be observed in all age groups starting in infancy. Stroke can lead to physical and intellectual disability.

●The risk of stroke can be reduced with appropriate screening and preventive therapy.

●Transcranial Doppler (TCD) screening is an important method to evaluate stroke risk [34]. The first TCD examination should be scheduled soon after the child's second birthday, and annual TCD screening should continue annually (or more frequently if abnormal TCD velocity or neurologic abnormalities are noted) through age 16, as permitted by bone windows [1]. (See "Prevention of stroke (initial or recurrent) in sickle cell disease", section on 'TCD screening protocol'.)

Detailed discussions of stroke prevention and management in patients with SCD are presented in separate topic reviews. (See "Prevention of stroke (initial or recurrent) in sickle cell disease" and "Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease" and "Hydroxyurea use in sickle cell disease".)

Priapism — Priapism, defined as a prolonged painful erection unrelated to sexual stimulation, occurs commonly in male children and adolescents with SCD. Parents or caregivers should receive education about the risk of priapism beginning before the child is two years old, with reinforcement at subsequent visits. This is particularly important for boys with Hb SS and Hb S-β⁰ thalassemia.

Key points to convey to the patient and caregivers include:

●Priapism is a painful, persistent erection unrelated to sexual stimulation, typically lasting 30 minutes or longer. It is a type of painful compartment syndrome. Like other painful events in SCD, it is caused by vaso-occlusion in the vasculature of the penis.

●There are two patterns of priapism:

•Stuttering priapism – These are brief episodes of priapism that may occur daily. Stuttering priapism and its management strategies can be addressed during regularly scheduled visits with the SCD clinician.

•Prolonged (also called major or acute episodes) – These are episodes of priapism lasting over four hours, and they may result in ischemia and permanent penile damage [35]. A patient with an episode of priapism lasting four hours or longer should seek immediate medical attention to minimize the chance of permanent vascular damage to the penis, which may lead to impotence [36].

Priapism in patients with SCD is discussed in greater detail separately. (See "Priapism and erectile dysfunction in sickle cell disease".)

Potentially curative therapies — As discussed above, hydroxyurea is the principal disease-modifying therapy for SCD and should be offered to all children with Hb SS or Hb S-β⁰ thalassemia beginning at the age of nine months. (See 'Hydroxyurea and other disease-modifying therapies' above.)

Another option that should be discussed periodically with families in the context of routine visits is hematopoietic stem cell transplantation (HCT), which is the only curative treatment for SCD. HCT has been available since the 1990s; however, the small but real risks of death and sterility from the procedure have limited its use. Parents or caregivers of children with Hb SS and Hb S-β⁰ thalassemia should be advised of this option and consideration given to human leukocyte antigen (HLA) typing of patient and full siblings at any time in childhood. (See "Hematopoietic stem cell transplantation in sickle cell disease".)

Modifications of HCT such as gene therapy are also under investigation. (See "Investigational therapies for sickle cell disease", section on 'Gene therapy and gene editing' and "Hematopoietic stem cell transplantation in sickle cell disease".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sickle cell disease and thalassemias".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: When your child has sickle cell disease (The Basics)")

PATIENT PERSPECTIVE TOPIC — Patient perspectives are provided for selected disorders to help clinicians better understand the patient experience and patient concerns. These narratives may offer insights into patient values and preferences not included in other UpToDate topics. (See "Patient perspective: Sickle cell disease".)

SUMMARY AND RECOMMENDATIONS

●Multidisciplinary care – All infants and children with sickle cell disease (SCD) should be managed by or in consultation with a clinician with special expertise in SCD. Depending upon local resources, the experienced SCD clinician may be a pediatric hematologist (often within a specialized SCD program) or a knowledgeable general pediatric provider. Children with SCD can have complications involving many different organ systems, and they often require involvement from multiple subspecialists. It is imperative to appropriately coordinate care when multiple specialists are involved. (See 'Multidisciplinary care' above.)

●Initial visit – The timing of the first visit with an experienced SCD clinician depends upon the hemoglobin (Hb) pattern on the newborn screen. Those with Hb SS or Hb S-β⁰ thalassemia should be seen by age six to eight weeks to begin prophylactic penicillin. For those with other SCD variants, the first visit can be deferred until age 12 to 16 weeks depending on local resources. The initial visit includes laboratory testing, confirmation of the SCD diagnosis and type, determination of the need for prophylactic penicillin, and anticipatory guidance about common early SCD complications. Caregivers should be taught to evaluate for complications that require urgent treatment (table 2). (See 'Initial visit' above.)

●Follow-up visits – The frequency of follow-up visits varies depending upon SCD type, patient needs, other medical conditions, and available medical resources. Follow-up visits should generally address the following (see 'Follow-up visits' above):

•Clinical assessment – This includes measurements of growth, vital signs (including blood pressure), pulse oximetry, focused history, and physical examination including splenic palpation. (See 'Routine monitoring at all visits' above.)

•Laboratory testing – A complete blood count and reticulocyte count should be obtained at each visit. (See 'Routine monitoring at all visits' above.)

•Administration of immunizations as appropriate based upon age (figure 1 and algorithm 1A-B and table 6A-B). (See "Standard immunizations for children and adolescents: Overview" and "Pneumococcal vaccination in children", section on 'Immunization of high-risk children and adolescents' and "Meningococcal vaccination in children and adults", section on 'Immunization of persons at increased risk'.)

•Assessing ongoing need for penicillin prophylaxis and adjusting the dose if appropriate. (See 'Prophylactic penicillin' above.)

•Initiation of and titration of hydroxyurea. (See "Hydroxyurea use in sickle cell disease".)

•Screening for associated conditions and comorbidities as appropriate based on the child's age (table 7).

•Providing anticipatory guidance on common SCD-specific issues, including fever, painful episodes, splenic sequestration, acute chest syndrome (ACS), stroke, priapism in males, and contraceptive counselling in adolescents. (See 'Anticipatory guidance' above.)

●Disease-modifying treatment – All families should learn about the benefits of hydroxyurea and the possible role of hematopoietic stem cell transplantation (HCT). The indications, risks, and benefits of these treatments should be reviewed in detail when appropriate. (See 'Potentially curative therapies' above and "Hydroxyurea use in sickle cell disease" and "Disease-modifying therapies to prevent pain and other complications of sickle cell disease" and "Hematopoietic stem cell transplantation in sickle cell disease".)