Medical observation of the children of the first three years of life in a family practice physician

Medical observation of the children of the first three years of life in a family practice physician.

Principles of polyclinic children’s care organisation.

 

Medical-preventive health care is based on the general principles and includes:

• Combination of medical and presentive health care;

• Applicationof the prophylactic medical examination method;

• Sequence of outpatient and inpatient care;

• Stages of specialized medical care.

Organization of outpatient polyclinic care for children is regulated by the Order № 434 MH of Ukraine (20.11.2002)

Children’s polyclinic provides:

• Organization and implementation of the preventive health care measures complex.

• Medical consultation care for children in the clinic and at home.

• Medical preventive health care at pre-school and school institutions.

• Antiepidemic measures with SES.

• Legal protection of children.

Children’s polyclinic (outpatient department of the hospital, children is in particular) is a medical preventive health care institution,which its area provides:

• Organization and carrying out the complex of preventive measures to protect children population aged 0-18 years.

• Early detection of diseases, qualified and thorough examination and treatment of sick children.

• Carrying out measures for sanitary hygiene education of population, promotion of healthy lifestyles, including nutrition, increased physical activity, anti-smoking and other addictions.

• Providing medical and first aid for sick children at home, who because of their health and nature of the disease caot visit the clinic, organization of hospitals at home.

• In time hospitalization of people requiring hospital treatment, with the primary thorough examination of patients, according to the profile of the disease.

• Providing thorough emergency medical care for children with acute illness, injury, poisoning and other accidents.

• Organization and carring out prophylactic medical examination of the children population.

• Organization and carring out of preventive measures among children:

– Antenatal protection of the fetus (prenatal nursing of pregnant women together with entenal clinic);

– Dynamic medical control of healthy children;

– Preventive examinations and clinical examination of children in accordance with standard;

– Preventive vaccinations in accordance with the vaccination calendar;

– Supervision of milk and dairy dishes – distribution units;

– Educational activity among parents, teachers, caregivers and children on healthy lifestyles, disease prevention, addictions and trauma.

• Rehabilitative treatment involving medical specialists.

• Providing instruction and treatment in health care institutions of all levels (if needed).

• Disability for children under 16 and registration and submission of documents to establish disability certification for children older than 16 years.

• Providing compulsory medical examination of children’s homes, orphanages, boarding schools, temporary shelters and other institutions for children – orphans and children deprived of parental care in consultation with the regional departments of Education, guardianship, Labour, Family and Youth, guardians, and others.

• The transfer of children on reaching 18 years of age in the outpatient network for adults.

• Providing of the organization and carring out of primary medical examinations and filling in medical records for primary youths military medical records registration and preparing them for military service.

• Maintain in of accounting records according to standarts adopted by the mins try of Health, analysis of statistical data on the activities of clinics, including general morbidity, mortality, care of children

• Involvement of public funds of the area to assist the clinic.

• Measures to improve the training of doctors and nurses of clinic.

Health index – (number of children who have never suffered in the first year of life / number of children who reached one year of age) x 100;

Mortality of children aged 0 to 14 years – (the number of children who died aged 0 to 14 years old this year / average number of children in the population under 14 years) x 1000;

Incidence – (total number of newly reported diseases per year / average number of children in the population) x 1000;

Quality of  Prehospital – (number of cases the diagnosis differences in the direction of clinical diagnosis / number Diagnostic of discharged from hospital patients) x 100.

Children’s Clinic (outpatient department, pediatric clinic) begins medical monitoring of the future child since being informed by the antenatal clinic about its registration.

Home (Senior) nurse is in charge of organizational control on intime, within one week after registration  at the antenatal clinic patronage of the children’s clinic in the first thrimester of pregnancy.

The first meeting with pregnant women the has at home.

If while registering women are recognized of medium or high risk pregnancy, district nurse informs the district pediatrician and takes home first pre-natal nursing.

Content of the primary medical nursing.

– picking up total and general information on pregnancy;

– picking up information on the family, the relations,desired or undesired pregnancy, living conditions and solial standard of the family before new birth, ability to support pregnant women after giving birth;

– recommendations as to the healthy nutristion and possible allergic effect of some fod on the fetus, importance of the psycho-emotional state of the pregnant women, positive emotions, preparation for lactation;

– carrying out prenanal fetus pathology prevention;

– promoting of the future father and mother responsibility for the helthy pregnancy and the helth of newborn;

– family orientation on mutual interrelation and understanding, favourable family atmosphere, refusing from alchohol and smoking, passive smoking in particular, precausions on unprescribed medications.

– recommendations on the healthy life style of the family, respect and support of pregnant women, future mother and child.

Medical records are filled in the Medical Records of the future child. The date of nurcing is registered, thrimester, pregnancy period.

The second nursing is carried out during 32-36 weeks of pregnancy.

The nursing is carried out by the area pediatrician and nurse at home.

Medical staff explains the future mother the special importance of the 3rd trimester of pregnancy for normal delivery and completion of physiological fetal development and birth of a healthy baby.

The main purpose of patronage in the 3rd trimester is the children’s policlinic support is to pregnant women recommenoling to visit antenatal clinics weekly to prevent complications, enhanced control over the development of the fetus in the most crucial period of antenatal development, enhancing communication of children clinics with family.

Medical staff:

– Must be sure in readiness of a family before birth, gives guidance in purchasing necessary items for the child;

– Privides general recommendations similar to those given in the first and second trimester, on the importance of motor activity, mental peace;

– Is interested in the expected birthweight predicted by the antenatal clinic, provides recommendations on the preparation of the breast and body to sufficient lactation, housing for the newborn child, clothing, care items, hygiene, etc.;

– Pays particular attention to the role of breastfeeding for the development and health of the child and of the mother herselffor its providing;

– Stresses the need for weekly blood pressure control, health monitoring and need of immediate treatment and medical care in the case of complications;

– Focuses on the need to preserve before childbirth and during childbirth tempered mental and emotional stations and believe in a favorable outcome;

– Stresses the need for early application of the newborn to the breast after birth, for which almost no contraindications are available;

– Reveals a family of antisocial behavior and submits written information to the head of the outpatient department to information the immediately minors and authorities the Board of Trustees in order to solve the future of the child.

Data on the second nursing and their recommendations are recorded by the area pediatrician and the nurse in the Medical Records of the future child.

 

Scheme of multiplicity mandatory medical preventive examinations of the child population

 

Comprehensive estimation of the children health includes: a) the functional state of organs and systems;

b) resistance and reactivity;

c) level and physical and neuropsychiatric development harmony;

d) availability of chronic (including congenital) disorders.

The functional state of organs and systems:

• is evaluated according to clinical examination, laboratory and instrumental methods of examination, basing on the analysis of behavior and adaptive abilities of the child.

• normal;

• impaired in some aspects (systems);

• bad – disordes in several organs and systems.

Resistance and reactivity:

• measured by the number of episodes of acute illness during the year;

• under monitoring a child less than a year – relation of the acute diseases wich the child had to the number of months of control.

Evaluation of resistance:

• satisfactory – up to 4 times a year;

• reduced – 4-7 illnesses per year;

• low – more than 7 diseases annually.

Physical development: a combination of morphological and functional characteristics of the body that characterize growth, weight, body shape, its structural and morphological properties. Objective measure of health, which is a result of the interaction of genetic factors and environmental factors.

Criteria for estimation of the physical development:

• Body weight;

• Body length (height);

• head ciroumference;

• chest ciroumference;

• Proportion of these indicators.

Estimation of physical development of the child is carried out by comparing its individual anthropometric indicators with standard. 2 main methods are used:

• method of approximate calculations;

• method anthropometric standards.

 

Head ciroumference:

At birth – 34-36 cm;

By 6 months. – 1.5 cm per month;

After 6 months. – 0.5 cm per month.

Up to 5 years – 1 cm annually.

Up to 15 years – 0.6 cm annually.

Chest ciroumference:

32-34 cm at birth;

First half-year – 2 cm per month;

Second half-year – to 0.5 cm per month;

Up to 10 years – 1.5 cm per year;

Up to 15 years – 3 cm annually.

 

Method anthropometric standards:

Anthropometric data of the child compared with regional age and sex tables standards.

Two types:

  – Sigmoid;

  – Tsentilo.

Cental method:

Comprehensive estimation of the physical development (height, weight are presented in interrelation);

Cental divides the range of values ​​of physical disorders into 100 equivalent intervals;

To characterize the physical development using 3, 10, 25, 50, 75, 90, 97 Tsentilo are used.

Sigma method:

Sigma tables are presented by the average arithmetic value of growth, body weight, other indicators of physical development and standard deviation;

Disadvantage of these tables – they do not give an idea of ​​the relationship of weight, height, and other parameters.

Assessment of physical development:

Medium – corresponds age norms in this area:

± 1 Ϭ;

25-75 Tsentilo;

7% – according to empirical formulas.

Below average:

  – 1-2 Ϭ; 25-10 Tsentilo; 8-20%.

above average:

+ 1-2 Ϭ; 75-90 Tsentilo; 8-20%.

low:

-> 2 Ϭ; 10-3 Tsentilo,> 20%.

high:

  +> 2 Ϭ; 90-97 Tsentilo,> 20%.

 

Harmonig (proportionality) physical development – if the number of columns of all anthropometric data are similare, or the difference between any two of them is not more than one column;

Disharmony – if the difference between the numbers of two columns is more than two.

Criteria for evaluating neuropsychological development of the child:

motility;

statics;

condition reflex activity;

language;

higher nervous activity.

Motility – a purposeful, manipulative activities of the child.

Newborn and physiological muscular hypertonicity, bending posture, movements are limited, chaotic, atetozopodibni.

2-nd-3d week – sight fixing

Fourth month. – Manual activity of hands;

4-5 months. – movement coordination of back muscles – turning;

1 year – coordinated purposeful movements of all muscles.

Statics – fixing and maintaining of certain parts of the body in desired position.

3 months – head holding;

6 -7 months. – Sitting, crawling;

9-10 months. – standing;

1 year – walking.

Condition reflex activity – the child is respond to the factors of the environment and oweeds.

Main dominant/- food;

At the end of the 1st month. – Watehes the mother’s face;

Second month – shaped smile;

4-5 months. – Animation complex;

5 months. – Oral attention;

8.9 months. – Pulling the arms to the mother, the reaction of fear and negativity to strangers.

Auditory and visual concentration.

Language

appears at 4-6 weeks – mumbling;

6 months. – Pronounces separate syllables – babbling;

1 year – 8-12 words;

2 years – simple sentences.

Evaluation of unconciouse reflexes:

strong;

transient;

constituent.

Persistent reflexes – available throughout the life:

swallowing;

tendon reflexes of the extremities;

corneal;

conjunctival;

superciliary.

Transient reflexes – available after birth, gradually disappear until a certain age.

Oral:

Sucking reflex;

Search Kussmaul reflex;

Rhopalocera reflex;

Palmar-mouth Babkin reflex.

Spinal reflexes of newborn:

Defence reflex;

Support reflex;

Automatic walk Reflex;

Grasping reflex (Robinson’s response);

Moro’s reflex;

Crawling Reflex (Bauer’s response);

Babinski’s sign (reflex);

Innervation of trunk response (Galant’s response);

Peres’s response.

Righting reflex:

No after birth, is formed at a certain age:

– Top Landau is reflex;

– Lower Landau is reflex.

Evaluation of neuro-psychological development of his age; leg behind in the development ahead of development.

1 year children – mastering skills ± 15 days;

After 1 year – all skills within 1 quarter.

The presence of chronic or congenital diseases

Infants groups at risk:

Group 1 – infants with risk of developing CNS pathology;

Group 2 – newborn with the risk of fetal infection;

Group 3 – infants with risk of venous disorders development;

Group 4 – newborns with risk for congenital malformations of organs and systems, and hereditary-related diseases;

Group 5 – newborns of social risk.

 

The frequency of examination by specialists:

• Neurologist – in 1 month (if needed-earlier, then – according to his recommendations;

• Oculist – when hypertension-hydrocephalic syndrome is suspected, according to the recommendations of neurologist, futher –  according to adopted terms;

• Orthopedist – when SSC, torticollis are suspected – to 2 months

• ENT doctor audiologist – under hearing impairment and speech disturfance;

• Logopedist – with signs of future speech disorders, low festivities activity, no babbling – 9-12 months.;

• Teacher, psychologist – in violation behavior, sleepdisturbance;

• Cardiologist – with vegetative-visceral disorders.

• Laboratory and instrumental examinations:

Thorough estimation of neurologic state of a newborn;

Posture, physical activity, weight gain, response on sound and light, the condition of the cranial sutures, the rate of psychomotor development;

Control of the dynamics of head sizes – up to a year;

Under suspicion VUI – PCR ELISA.

 

 

Clinical protocol on the infants care

 

Clinical protocol is the basic and is designed to provide measures for forming, maintaining and improving the health of infants (up to three years of life). The protocol is based on the concept of an integrated approach to the infants health care by establishing the relationship between the providing of medical aid due to the disease prevention, as well as family involvement in the infants care which results in the comprehensive development. The protocol describes the terms and scope of mandatory preventive examinations of infants under three years, standards of care efficient feeding and nutrition, control, estimation of physical and psychomotor development specific prevention, purpeseful consultations. If any abnormalities in the infants health were found additional medical invasation, according to current medical protocols. Infants care since the birth to the discharge from the hospital are carriedout conducted according to Order of Ministry of Helth Care of Ukraine № 152 of 04.04.2005.

 

1.1 Purpose and objectives of the protocol

  Protocol “Protocol of care and medical supervision of infants,” is created to improve medical care for children in outpatient conditions by streamlining the examination of a child, reducing invasive interventions. Particular attention is paid to monitoring of the physical development of children, nutrition estimation, consultation of parents on child care. Principles of control and recommendations contained in the protocol, are focused on the active involvement of the family in the process of care for the infants and informing parents who take care of them.

 

2. Preventive examinations of infants under 3 years

   

  Definition: preventive examinations – a systems of measures directed at the prevention and detection of diseases at the early stages as well as carrying out medical – prevention, measures family instructing for maintaining and improving the health of children. Preventive examinations are obligatory and are held in a defined time terms. Preventive examinations are conducted in order to:

• evaluate the health state of a child;

• detect diseases and pathology on time;

  • evaluate physical and psychomotor development of a child;

• evaluate nutrition;

• control vaccination;

 

• instruct parents on: child care, nutrition, child development, prevention of accidents and injuries;

• develop recommendations and a plan for further control and examination of the child.

2.1 Organizational conditions of preventive examinations

 

Preventive examinations can be carried out in outpatient – polyclinic health, preschool child care centers, children’s homes, as well as at home. Review conducted in the presence of parents (guardians), in a comfortable environment for the child, at or below 20 ° C, with adequate lighting. Necessary equipment for the office routine inspection are presented in Appendix 1.

2.2 Frequency of healthy child examination

The protocol provides the following minimum number of preventive examinations from birth to 3 years of age: 11 medical checkups and 6 control by nurses (Table 1). The doctor can increase the number of examination if the child requires more frequent monitoring. Unreasonable increase in the number of examinations does not result in the improve ment of the child’s helth. [A].

 

2.3 Major components of the prethentive health care examination

2.3.1 Medical History

It is requiredto meet with a child family and gather his history. Availability of full information about the child enables medicals to detect the disease on time or to prevent it. You must collect: obstetric history (pregnancy and childbirth), information on the presence of genetic, socially dangerous diseases in the family (VIL. tuberculosis, etc.), allergy history and to get information the addicts of parents.

 

It is required to find out if there are any problems related to the unproper social behavior. When social problems are confirmed social worker and relevant organizations: (Juvenile Family Service) should be informed.

 

2.3.2 Examination of organs and systems

Estimation of the health of a child according to the examination of organs  and systems is carried out during each preventive examination. General examination of children of different age groups has its own characteristics, which are listed in Table 2. If there are deviations, to estimate the health of the child the doctor can increase the frequency of visits or appoint the additional examination.

a) Nutrition estimation[C]

Estimation of infants feeding is carried out during each checkups. It can be made by both doctors and nurses followed by instruction mothers and families on a child nutrition.

b) Estimation of physical development [A]

Estimation of the physical development of the child is held during every checkup. The following anthropometric measurements are carried out: weighing, measuring of length / height and head circumference. The obtained data are plotted on the relevant schems of physical development, which are filled in separately for boys and girls (Apendix 16).

c) Estimation of psychomotor development [A]

Estimation of the psychomotor development of the child is held during every checkups. Methods of estimation of psychomotor development and interpretation of the results are set forth in the “psychomotor development.” After estimation of the psychomotor development conducted mothers are istructed on child’s development.

d) Monitoring and carrying out vaccination

Control of the vaccination is performed during each preventive examinations and filling in relevant documentation.

 

Medical report on the health of a child is defined by the term “healthy”, and when disease or injury are detected,they are specified. Nowadays it is not worthy distributing children into health groups and risk groups. Similar attention should be paied to every child. If there are deviations the doctor can develop an individual plan of preventive examinations of the child.

Identification of risk groups according to obstetric history is also recommended practical. Time-table of the preventive health care examination for this group is defined individualy.

Defined only risk with social factors. Plan of preventive checkups for children of this group is determined individually.

 

2.3.4 Parents instructing [A]

 During each preventive health care instructing of parents is carried out. Snstructing is conducted in accordance with the principles of effective teaching. Principles of effective instructing are presented in Appendix 2. Topic instucting depends on the age of the child and problems identified.

 

2.3.5 Examination of narrow specialist doctors and additional.

Additional examinations (laboratory, instrumental, professional advice) are held only if needed. Every medical intervention, examinations of narrow specialist should be reasonable and safe for the baby and held provided the mother was informed. At present there is no scientific evidence base for routine laboratory studies and other surveys of a healthy baby up to 9 months of life. Laboratory examinations conducted for children aged 9 months: hemoglobin level inblood to detect anemia [C], and urinalysis. In the age of 12 months to detect retinal pathology examination by an oculist is carried out and examination by a dentist to detect bite pathology. At the age of 3 years the analysis of feces for the presence of worms and scraping on enterobiasis.

 

Schedule of the preventive health care examination

 

 

 

 

 

Iron deficiency anemia – children

Anemia is a condition in which the body does not have enough healthy red blood cells. Red blood cells bring oxygen to body tissues.

There are many types of anemia. Iron deficiency anemia is a decrease in the number of red blood cells in the blood due to a lack of iron.

Causes

Iron deficiency anemia is the most common form of anemia. You get iron through certain foods, and your body also reuses iron from old red blood cells.

Iron deficiency (too little iron) may be caused by:

• An iron-poor diet (this is the most common cause)

• Body not being able to absorb iron very well, even though you’re eating enough iron

• Long-term, slow blood loss — usually through menstrual periods or bleeding in the digestive tract

• Rapid growth (in the first year of life and in adolescence), when more iron is needed

Babies are born with iron stored in their bodies. Because they grow rapidly, infants and children need to absorb an average of 1 mg of iron per day.

Since children only absorb about 10% of the iron they eat, most childreeed to receive 8-10 mg of iron per day. Breastfed babies need less, because iron is absorbed 3 times better when it is in breast milk.

Cow’s milk is a common cause of iron deficiency. It contains less iron than many other foods and also makes it more difficult for the body to absorb iron from other foods. Cow’s milk also can cause the intestines to lose small amounts of blood.

The risk of developing iron deficiency anemia is increased in:

• Infants younger than 12 months who drink cow’s milk rather than breast milk or iron-fortified formula

• Young children who drink a lot of cow’s milk rather than eating foods that supply the body with more iron

Iron deficiency anemia most commonly affects babies 9 – 24 months old. All babies should have a screening test for iron deficiency at this age. Babies born prematurely may need to be tested earlier.

Iron deficiency in children also can be related to lead poisoning.

Symptoms

• Blue-tinged or very pale whites of eyes

• Blood in the stools

• Brittle nails

• Decreased appetite (especially in children)

• Fatigue

• Headache

• Irritability

• Pale skin color (pallor)

• Shortness of breath

• Sore tongue

• Unusual food cravings (called pica)

• Weakness

Exams and Tests

The health care provider will perform a physical exam. A blood sample is taken and sent to a laboratory for examination. Iron-poor red blood cells appear small and pale when looked at under a microscope.

Tests that may be done include:

• Hematocrit

• Serum ferritin

• Serum iron

• Total iron binding capacity (TIBC)

A measurement called iron saturation (serum iron/TIBC) often can show whether you have enough iron in your body.

Diagnosis of Iron Deficiency Anemia

Figure 1.

Diagnostic algorithm for iron deficiency anemia. (MCV = mean corpuscular volume; LR+ = positive likelihood ratio; TIBC = total iron-binding capacity; FE = serum iron; TfR = serum transferrin receptor.)

Adapted with permission from Ioannou GN, Spector J, Scott K, Rockey DC. Prospective evaluation of a clinical guideline for the diagnosis and management of iron deficiency anemia. Am J Med 2002;113:281–7.

 

Treatment

Treatment involves iron supplements (ferrous sulfate), which are taken by mouth. The iron is best absorbed on an empty stomach, but many people need to take the supplements with food to avoid stomach upset. Another way to increase iron absorption is to take it together with vitamin C.

If you cannot tolerate iron supplements by mouth, you may get iron by injection into a muscle or through a vein (IV).

Milk and antacids can interfere with iron absorption and should not be taken at the same time as iron supplements.

Iron-rich foods include raisins, meats (especially liver), fish, poultry, egg yolks, legumes (peas and beans), and whole-grain bread.

Outlook (Prognosis)

With treatment, the outcome is likely to be good. In most cases, the blood counts will return to normal in 2 months. It is essential to determine the cause of the iron deficiency. If it is being caused by blood loss other than monthly menstruation, further investigation will be needed.

You should continue taking iron supplements for another 6 to 12 months after blood counts return to normal, or as your health care provider recommends. This will help the body rebuild its iron storage.

Iron supplementation improves learning, memory, and cognitive test performance in adolescents who have low levels of iron. Iron supplementation also improves the performance of athletes with anemia and iron deficiency.

Possible Complications

Iron deficiency anemia can affect school performance. Low iron levels are an important cause of decreased attention span, reduced alertness, and learning difficulties, both in young children and adolescents.

Excess amounts of lead may be absorbed by people with iron deficiency.

Prevention

The American Academy of Pediatrics (AAP) recommends that all infants be fed breast milk or iron-fortified formula for at least 12 months. The AAP does NOT recommend giving cow’s milk to children under 1 year old.

Diet is the most important way to prevent and treat iron deficiency.

Good sources of iron include:

• Apricots

• Kale and other greens

• Oatmeal

• Prunes

• Raisins

• Spinach

• Tuna

Better sources of iron include:

• Chicken and other meats

• Dried beans and lentils

• Eggs

• Fish

• Molasses

• Peanut butter

• Soybeans

• Turkey

The best sources of iron include:

• Baby formula with iron

• Breast milk (the iron is very easily used by the child)

• Infant cereals and other iron-fortified cereals

• Liver

• Prune juice

Anemia is a disorder in which there are too few red blood cells in the blood.

·                     Anemia can occur when red blood cells are broken down too rapidly, too much blood is lost, or the bone marrow does not produce enough red blood cells.

·                     If red blood cells are broken down too rapidly, levels of bilirubin increase, and the newborn’s skin and the whites of the eyes appear yellow (jaundice).

·                     If a large amount of blood is lost very rapidly, the newborn may be in shock, appear pale, have a rapid heart rate, and have low blood pressure along with rapid, shallow breathing.

·                     If there is less severe blood loss or the blood is lost gradually, the newborn appears normal but pale.

·                     Treatment may involve fluids given by vein (intravenously) followed by a blood transfusion or an exchange blood transfusion.

Normally, the bone marrow does not produce new red blood cells between birth and 3 or 4 weeks of age, causing a slow drop in the red blood cell count (called physiologic anemia) over the first 2 to 3 months of life. Very premature newborns have a slightly greater drop in red blood cell count. More severe anemia can occur when

·                     Red blood cells are broken down too rapidly

·                     A lot of blood is taken from preterm infants for blood tests

·                     Too much blood is lost during labor or delivery

·                     The bone marrow does not produce blood cells

More than one of these processes can occur at the same time.

Severe red blood cell breakdown results in anemia and high levels of bilirubin in the blood (hyperbilirubinemia). Hemolytic disease of the newborn may cause the newborn’s red blood cells to be destroyed rapidly. The red blood cells may also be rapidly destroyed if the newborn has a hereditary abnormality of the red blood cells. An example is hereditary spherocytosis, in which the red blood cells look like small spheres when viewed under a microscope. Another rare example occurs in some infants who lack a specific red blood cell enzyme (glucose-6-phosphate dehydrogenase [G6PD]. In these infants, exposure of the mother and fetus to certain drugs used during pregnancy (such as aniline dyes, sulfa drugs, and many others) may result in rapid breakdown of red blood cells.

Infections acquired before birth, such as toxoplasmosis, rubella, cytomegalovirus infection, herpes simplex virus infection, or syphilis, may also rapidly destroy red blood cells, as can bacterial infections of the newborn acquired during or after birth.

Blood loss is another cause of anemia. Blood loss can occur in many ways. For example, blood is lost if there is a large transfusion of fetal blood across the placenta (the organ that connects the fetus to the uterus and provides nourishment to the fetus) and into the mother’s circulation (fetal–maternal transfusion) or if too much blood gets trapped in the placenta at delivery, when the newborn is held above the mother’s abdomen when the umbilical cord is clamped. Twin-to-twin transfusions, in which blood flows from one fetus to the other, can cause anemia in one twin and too much blood (polycythemia) in the other twin. The placenta may separate from the uterine wall before delivery (placental abruption), leading to hemorrhage of fetal blood.

Rarely, failure of the fetal bone marrow to produce red blood cells may result in anemia. Examples of this lack of production include rare genetic disorders such as Fanconi’s anemia and Diamond-Blackfan anemia. Some infections (such as cytomegalovirus infection, syphilis, and HIV) also prevent the bone marrow from producing red blood cells.

Symptoms and Diagnosis

Most infants with mild or moderate anemia have no symptoms. Moderate anemia may result in sluggishness (lethargy), poor feeding, or no symptoms. Newborns who have suddenly lost a large amount of blood during labor or delivery may be in shock and appear pale and have a rapid heart rate and low blood pressure, along with rapid, shallow breathing. When the anemia is a result of rapid breakdown of red blood cells, there is also an increased production of bilirubin, and the newborn’s skin and whites of the eyes appear yellow (jaundice). Diagnosis is based on symptoms and is confirmed with blood tests.

Treatment

Most infants have mild anemia and do not require any treatment.

Newborns who have rapidly lost large amounts of blood, often during labor and delivery, are treated with intravenous fluids followed by a blood transfusion. Very severe anemia caused by hemolytic disease may also require a blood transfusion, but the anemia is more often treated with an exchange blood transfusion, which lowers the bilirubin level as well as increases the red blood cell count. In an exchange transfusion, a small amount of the newborn’s blood is gradually removed (one syringe at a time) and replaced with equal volumes of fresh donor blood.

 

Hemolytic disease of the newborn (also called erythroblastosis fetalis or eythroblastosis neonatorum) is a condition in which red blood cells are broken down or destroyed more rapidly thaormal, causing hyperbilirubinema, anemia, and, in the most severe forms, death. Hemolytic disease of the newborn may occur in Rh-positive babies born to Rh-negative mothers. It develops when the newborn’s red blood cells are destroyed by anti-Rh antibodies that were produced by the mother and passed through the placenta from the mother’s circulation into the fetal circulation before delivery. A mother who is Rh-negative can produce antibodies against Rh-positive blood cells if she was previously exposed to red blood cells from a fetus that was Rh-positive. Such exposure may occur during pregnancy or labor, but it may also occur if the mother had been accidentally transfused with Rh-positive blood at any time earlier in life.

The mother’s body then responds to the “incompatible” blood by producing antibodies to destroy the “foreign” Rh-positive cells. These antibodies cross the placenta during a subsequent pregnancy. If the fetus she is carrying is Rh-negative, there is no consequence. However, if the fetus has Rh-positive red blood cells, the mother’s antibodies attach to and start to destroy the fetal red blood cells, leading to anemia of varying degrees. The rapid breakdown of red blood cells begins in the fetus and continues after delivery.

Severe anemia caused by hemolytic disease of the newborn is treated in the same way as any other anemia. Doctors also observe the newborn for jaundice, which is likely to occur because hemoglobin from the red blood cells that are being rapidly broken down is converted to the yellow pigment bilirubin, giving the newborn’s skin and whites of the eyes a yellow appearance. Jaundice can be treated by exposing the newborn to bright lights (phototherapy) or by having the newborn undergo an exchange blood transfusion. Very high levels of bilirubin in the blood can lead to brain damage (kernicterus), unless it is prevented by these measures.

To prevent sensitization of Rh-negative women, the Rh antigen, an Rh₀(D) immune globulin preparation, is given by injection at about 28 weeks of pregnancy and again immediately after delivery. Injection of this immune globulin prevents the mother’s immune system from producing anti-Rh antibodies, and it also rapidly coats any Rh-positive fetal red blood cells that have entered the mother’s circulation so they are not recognized as Rh-positive cells by the mother’s immune system. This treatment usually prevents hemolytic disease of the newborn from developing.

Sometimes other blood group incompatibilities may lead to similar (but milder) hemolytic diseases. For example, if the mother has blood type O and the fetus has blood type A or B, then the mother’s body produces anti-A or anti-B antibodies that can cross the placenta, attach to fetal red blood cells, and cause their breakdown (hemolysis), leading to mild anemia and hyperbilirubinemia. Rh incompatibility usually leads to more severe anemia than ABO incompatibility.

 

Rickets

Rickets is a disease of growing bone that is unique to children and adolescents. It is caused by a failure of osteoid to calcify in a growing person. Failure of osteoid to calcify in adults is called osteomalacia.

Vitamin D deficiency rickets occurs when the metabolites of vitamin D are deficient. Less commonly, a dietary deficiency of calcium or phosphorus may also produce rickets. Vitamin D-3 (cholecalciferol) is formed in the skin from a derivative of cholesterol under the stimulus of ultraviolet-B light. Ultraviolet light or cod liver oil was the only significant source of vitamin D until early in the 20th century when ergosterol (vitamin D-2) was synthesized from irradiated plant steroids.

During the Industrial Revolution, rickets appeared in epidemic form in temperate zones where the pollution from factories blocked the sun’s ultraviolet rays. Thus, rickets was probably the first childhood disease caused by environmental pollution.

Natural nutritional sources of vitamin D are limited primarily to fatty, ocean-going fish. In the United States, dairy milk is fortified with vitamin D (400 IU/L) Human milk contains little vitamin D, generally less than 20-40 IU/L. Therefore, infants who are breastfed are at risk for rickets, especially those who receive no oral supplementation and those who have darkly pigmented skin, which blocks penetration of ultraviolet light.

Rickets may lead to skeletal deformity and short stature. In females, pelvic distortion from rickets may cause problems with childbirth later in life. Severe rickets has been associated with respiratory failure in children.

Pathophysiology

Cholecalciferol (ie, vitamin D-3) is formed in the skin from 5-dihydrotachysterol. This steroid undergoes hydroxylation in 2 steps. The first hydroxylation occurs at position 25 in the liver, producing calcidiol (25-hydroxycholecalciferol), which circulates in the plasma as the most abundant of the vitamin D metabolites and is thought to be a good indicator of overall vitamin D status.

The second hydroxylation step occurs in the kidney at the 1 position, where it undergoes hydroxylation to the active metabolite calcitriol (1,25-dihydroxycholecalciferol). This cholecalciferol, which circulates in the bloodstream in minute amounts, is not technically a vitamin but a hormone.

Calcitriol acts at 3 known sites to tightly regulate calcium metabolism: (1) it promotes absorption of calcium and phosphorus from the intestine; (2) it increases reabsorption of phosphate in the kidney; and, (3) it acts on bone to release calcium and phosphate. Calcitriol may also directly facilitate calcification. These actions result in an increase in the concentrations of calcium and phosphorus in extracellular fluid.

This increase of calcium and phosphorus in extracellular fluid, in turn, leads to the calcification of osteoid, primarily at the metaphyseal growing ends of bones but also throughout all osteoid in the skeleton. Parathyroid hormone facilitates the 1-hydroxylation step in vitamin D metabolism.

In the vitamin D deficiency state, hypocalcemia develops, which stimulates excess secretion of parathyroid hormone. In turn, renal phosphorus loss is enhanced, further reducing deposition of calcium in the bone.

Excess parathyroid hormone also produces changes in the bone similar to those occurring in hyperparathyroidism. Early in the course of rickets, the calcium concentration in the serum decreases. After the parathyroid response, the calcium concentration usually returns to the reference range, though phosphorus levels remain low. Alkaline phosphatase, which is produced by overactive osteoblast cells, leaks into the extracellular fluids, so that its concentration rises to anywhere from moderate elevation to very high levels.

Intestinal malabsorption of fat and diseases of the liver or kidney may produce the clinical and secondary biochemical picture of nutritional rickets. Anticonvulsant drugs (eg, phenobarbital, phenytoin) accelerate metabolism of calcidiol, which may lead to insufficiency and rickets, particularly in children who who have darkly pigmented skin and those who are kept primarily indoors (eg, children who are institutionalized).

Calcium and vitamin D intakes are low in infants who are fed vegan diets, particularly in those who are lactovegans, and monitoring of their vitamin D status is essential.

Studies have noted that disorders of increased fibroblast growth factor 23 (FGF-23) function are associated with rickets.

Physical Examination

Generalized muscular hypotonia of an unknown mechanism is observed in most patients with clinical (as opposed to biochemical and radiographic) signs of rickets. Craniotabes (areas of thinning and softening of bones of the skull) manifests early in infants with vitamin D deficiency, although this feature may not be present in infants, especially those born prematurely.

If rickets occurs at a later age, thickening of the skull develops. This produces frontal bossing and delays the closure of the anterior fontanelle. In the long bones, laying down of uncalcified osteoid at the metaphases leads to spreading of those areas, producing knobby deformity, which is visualized on radiography as cupping and flaring of the metaphyses.

Weight bearing produces deformities such as bowlegs and knock-knees.

In the chest, knobby deformities results in the so-called rachitic rosary along the costochondral junctions. The weakened ribs pulled by muscles also produce flaring over the diaphragm, which is known as Harrison groove. The sternum may be pulled into a pigeon-breast deformity.

In more severe instances in children older than 2 years, vertebral softening leads to kyphoscoliosis. The ends of the long bones demonstrate that same knobby thickening. At the ankle, palpation of the tibial malleolus gives the impression of a double epiphysis (Marfan sign). Because the softened long bones may bend, they may fracture on one side of the cortex (ie, greenstick fracture).

Manifestations of rickets are illustrated in the image below.

Findings in patients with rickets.

Diagnostic Considerations

Rare metabolic bone diseases, including hypophosphatasia, have been confused with rickets in infancy. Jansen syndrome is a rare autosomal dominant form of short-limbed dwarfism in which infants present with metaphyseal chondroplasia. Hereditary disorders of vitamin D metabolism have also been described, such as hypophosphatemic vitamin D–resistant rickets.

Severe calcium deficiency can also cause a syndrome that is confused with vitamin D deficiency rickets. Premature infants who are breast fed and do not receive mineral supplements may develop severe phosphorus deficiency that presents as rickets.

Approach Considerations

Serum measurements in the workup for rickets may include the following:

• Calcium

• Phosphorus

• Alkaline phosphatase

• Parathyroid hormone

• 25-hydroxy vitamin D

• 1,25-dihydroxyvitamin D

Serum Chemistry

Early on in the course of rickets, the calcium (ionized fraction) is low. However, this level is often within the reference range at the time of diagnosis, as a consequence of increased parathyroid hormone secretion.

Although calcidiol (25-hydroxy vitamin D) is low and parathyroid hormone is elevated, determining calcidiol and parathyroid hormone levels is typically not necessary in order to establish a diagnosis.

Calcitriol levels maybe normal or elevated because of increased parathyroid activity.

The phosphorus level is invariably low for age, unless recent partial treatment or recent exposure to sunlight has occurred. Alkaline phosphatase levels are uniformly elevated.

A generalized aminoaciduria occurs from the parathyroid activity. However, aminoaciduria does not occur in familial hypophosphatemia rickets (FHR).

Radiography

The best single radiographic view for infants and children younger than 3 years is an anterior view of the knee that reveals the metaphyseal end and epiphysis of the femur and tibia. This site is best because growth is most rapid in this location, thus the changes are accentuated.

The metaphyses exhibit widening and cupping because of their exaggerated normal concavity and irregular calcification. Because calcified osteoid is abundant, the provisional calcification zone of the metaphysis is much more distant from the calcification center of the epiphysis than is normal for age.

Along the shaft, the uncalcified osteoid causes the periosteum to appear separated from the diaphysis. Generalized osteomalacia occurs (observed as osteopenia), with visible coarsening of trabeculae in contrast to the ground-glass osteopenia of scurvy.

Examples of radiographic findings are shown in the images below.

Anteroposterior and lateral radiographs of the wrist of an 8-year-old boy with rickets demonstrates cupping and fraying of the metaphyseal region.

 

Radiographs of the knee of a 3.6-year-old girl with hypophosphatemia depict severe fraying of the metaphysis.

Approach Considerations

Treatment for rickets may be administered gradually over several months or in a single-day dose of 15,000 mcg (600,000 U) of vitamin D.^[5] If the gradual method is chosen, 125-250 mcg (5000-10,000 U) is given daily for 2-3 months until healing is well established and the alkaline phosphatase concentration is approaching the reference range. Because this method requires daily treatment, success depends on compliance.

If the vitamin D dose is administered in a single day, it is usually divided into 4 or 6 oral doses. An intramuscular injection is also available. Vitamin D (cholecalciferol) is well stored in the body and is gradually released over many weeks. Because both calcitriol and calcidiol have short half-lives, these agents are unsuitable for treatment, and they bypass the natural physiologic controls of vitamin D synthesis.

The single-day therapy avoids problems with compliance and may be helpful in differentiating nutritional rickets from familial hypophosphatemia rickets (FHR). In nutritional rickets, the phosphorus level rises in 96 hours and radiographic healing is visible in 6-7 days. Neither happens with FHR.

If severe deformities have occurred, orthopedic correction may be required after healing. Most of the deformities correct with growth.

A consultation with a pediatric endocrinologist is recommended.

Treatment for rickets is with cholecalciferol, which may be gradually administered over several months or in a single-day dose.^[5] The single-day therapy avoids problems with compliance and may be helpful in differentiating nutritional rickets from familial hypophosphatemia rickets (FHR). Iutritional rickets, the phosphorous level rises in 96 hours and radiographic healing is visible in 6-7 days. Neither happens with FHR.

Vitamin D is well stored in the body and is gradually released over many weeks. Because both calcitriol and calcidiol have short half-lives, they are unsuitable; they would bypass the natural physiologic controls of vitamin D synthesis.

Vitamin D

Class Summary

Vitamin D is a fat-soluble vitamin used to prevent or treat vitamin D deficiency.

View full drug information

Cholecalciferol (Vitamin D3, Ddrops Kids, Delta-D3)

For treatment of rickets, cholecalciferol can be given in a single-day dose of 15,000 mcg (600,000 U), which is usually divided into 4 or 6 oral doses. An intramuscular injection is also available.

An alternative regimen is to give 125-250 mcg (5000-10,000 U) daily for 2-3 months until healing is well established and the alkaline phosphatase concentration is approaching the reference range. Because this gradual method requires daily treatment, success depends on compliance.

 http://reference.medscape.com/

 

References

Glader B. Iron-deficiency anemia. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, Pa: Saunders Elsevier; 2007: chap 455.

Stettler N, Bhatia J, Parish A, Stallings VA. Feeding healthy infants, children, and adolescents. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics. 19th Ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 42.

O’Connor NR. Infant formula. Am Fam Physician. 2009;79:565-570.

Human Milk and Lactation

Breast milk is thought to be the best form of nutrition for neonates and infants. The properties of human milk facilitate the transition of life from in utero to ex utero. This dynamic fluid provides a diverse array of bioactive substances to the developing infant during critical periods of brain, immune, and gut development. The clinician must be familiar with how the mammary gland produces human milk and how its properties nourish and protect the breastfeeding infant.

Clinicians play a crucial role in a mother’s decision to breastfeed and can facilitate her success in lactation. Although a mother may not be aware of the evidence indicating that breast milk contributes to her baby’s short-term and long-term well-being, she has developed certain attitudes and cultural beliefs about breastfeeding. The issue of bonding between mother and newborn may be a strong factor; however, stronger cultural or societal barriers may result in the decision to formula feed. Such issues must be understood for successful counseling. The mother makes her decision regarding breastfeeding prior to delivery in more than 90% of cases; therefore, her choice of infant nutrition should be discussed starting in the second trimester and continue as part of an ongoing dialogue during each obstetric visit.

This article reviews the development of the mammary gland (mammogenesis), the process through which the mammary gland develops the capacity to secrete milk (lactogenesis), the process of milk production (lactation), and the specific properties of human milk that make it unique and appropriate for human infants. In a related article titled Counseling the Breastfeeding Mother, the mechanics of breastfeeding and evaluation of the breastfeeding mother-infant dyad are discussed. Such articles are intended to be overviews. For a more in-depth treatise, please refer to textbooks by Lawrence and Lawrence (2005) and the American Academy of Pediatrics (2006). Guidelines for breastfeeding and the use of human milk have been established by the American Academy of Pediatrics.

The breast begins to develop in utero, undergoing the first of many developmental changes necessary for proper breastfeeding to occur. A bulb-shaped mammary bud can be discerned in the fetus at 18-19 weeks’ gestation. Inside the bud, a rudimentary mammary ductal system is formed, which is present at birth. After birth, growth of the gland parallels that of the child until puberty. The normal anatomy of the mammary gland following pubertal development is shown in the images below.

 

 

 

Schematic diagram of the breast.

Frontal view of lactating breast.

The basic unit of the mammary gland is the alveolus or acinus cell that connects to a ductule. Each ductule was believed to independently drain to a duct that, in turn, emptied into lactiferous sinuses. These lactiferous sinuses drain to 15-25 openings in the nipple, allowing milk to flow to the recipient infant.

More recently, researchers such as Ramsay et al (2005) have questioned the existence of lactiferous sinuses.^[5] Extensive real-time ultrasonography of 21 fully lactating women provided better understanding of the anatomy of the lactating human breast, as shown below.

 

 

 

 (A) Ultrasound image of milk duct in the lactating breast. The duct appears as a branching hypoechoic structure within echogenic glandular tissue. (B) The ducts focused on the nipple (N) to the periphery of the breast. The walls are echogenic (up arrow) and the lumen hypoechoic (asterisk). The first branch of this duct (–>) is imaged almost directly under the nipple.

On ultrasonography, milk ducts appear as superficial, hypoechoic tubular structures with echogenic walls whose milk-fat globules appear as echoes. The ducts are easily compressed, do not display typical sinuses, and anatomically appear to transport the milk rather than store it.

The ducts can be traced from the base of the nipple back into the parenchyma. The meaumber of main ducts greater than 0.55 mm diameter at the base of the nipple was approximately 10 for the left breast and 9 for the right breast. Although the duct diameter was increased at multiple branch points, the typical saclike appearance of lactiferous sinuses under the areola was not observed during scanning. The meaumber of ducts and the diameter of the main ducts were not related to nipple diameter, areola radius, or milk production for individual breasts. Adipose and glandular tissue distribution differed widely among women but not between breasts. In addition, the proportion of glandular and fat tissue and the number and size of ducts were not related to milk production.

At puberty, released estrogen stimulates breast tissue to enlarge through growth of mammary ducts into the preexisting mammary fat pad. Progesterone, secreted in the second half of the menstrual cycle, causes limited lobuloalveolar development. The effects of estrogen and progesterone facilitate the formation of the characteristic structure of the adult breast, which is the terminal duct lobular unit. However, full alveolar development and maturation of epithelium requires the hormones of pregnancy.

Lactogenesis

In lactogenesis, the mammary gland develops the capacity to secrete milk. Lactogenesis includes all processes necessary to transform the mammary gland from its undifferentiated state in early pregnancy to its fully differentiated state sometime after pregnancy. This fully differentiated state allows full lactation. The 2 stages of lactogenesis are discussed below.

Stage 1 occurs by mid pregnancy. In stage 1, the mammary gland becomes competent to secrete milk. Lactose, total protein, and immunoglobulin concentrations increase within the secreted glandular fluid, whereas sodium and chloride concentrations decrease. The gland is now sufficiently differentiated to secrete milk, as evidenced by the fact that women often describe drops of colostrum on their nipples in the second or third trimester. However, high circulating levels of progesterone and estrogen hold the secretion of milk in check.

Stage 2 of lactogenesis occurs around the time of delivery. It is defined as the onset of copious milk secretion. In stage 2, blood flow, oxygen, and glucose uptake increase, and citrate concentration increases sharply. Increased milk citrate is considered a reliable marker for the second stage of lactogenesis. Progesterone plays a key role in this stage. Removal of the placenta (ie, the source of progesterone during pregnancy) is necessary for the initiation of milk secretion; however, the placenta does not inhibit established lactation. Work by Haslam and Shyamala reveals that progesterone receptors are lost in lactating mammary tissues, thus decreasing the inhibitory effect of circulating progesterone. In addition, maternal secretion of insulin, growth hormone (GH), cortisol, and parathyroid hormone (PTH) facilitates the mobilization of nutrients and minerals that are required for lactation.

The stages of lactation can be summarized as follows (adapted from Riordan and Auerbach, 1998):

• Mammogenesis: Mammary (breast) growth occurs. The size and weight of the breast increase.

• Lactogenesis

• Stage 1 (late pregnancy): Alveolar cells are differentiated from secretory cells.

• Stage 2 (day 2 or 3 to day 8 after birth): The tight junction in the alveolar cell closes. Copious milk secretion begins. Breasts are full and warm. Endocrine control switches to autocrine (supply-demand) control.

• Galactopoiesis (later than 9 d after birth to beginning of involution): Established secretion is maintained. Autocrine system control continues.

• Involution (average 40 d after last breastfeeding): Regular supplementation is added. Milk secretion decreases from the buildup of inhibiting peptides.

Lactation

• Two essential hormones (prolactin and oxytocin)

• During the second stage of lactogenesis, the breast becomes capable of milk production. For the ongoing synthesis and secretion of human milk, the mammary gland must receive hormonal signals. These signals, which are in direct response to stimulation of the nipple and areola (mammae), are then relayed to the central nervous system. This cyclical process of milk synthesis and secretion is termed lactation. Lactation occurs with the help of 2 hormones, prolactin (PRL) and oxytocin. Although PRL and oxytocin act independently on different cellular receptors, their combined actions are essential for successful lactation.

• Prolactin

• Milk synthesis occurs in the mammary gland epithelial cells in response to PRL activation of epithelial cell PRL receptors. PRL, a polypeptide hormone synthesized by lactotrophic cells in the anterior pituitary, is structurally similar to GH and placental lactogen (PL), which appear to have cytokine functions. The secretion of PRL appears to be both positively and negatively regulated; however, its main locus of control comes from hypothalamic inhibitory factors, the most important of which is dopamine, acting through the D2 subclass of dopamine receptors present in lactotrophs. PRL stimulates mammary glandular ductal growth and epithelial cell proliferation and induces milk protein synthesis.

• Research during the past several decades has led to a deeper understanding of PRL’s role in the body. PRL-related knockout models support PRL’s pivotal role in lactation and reproduction, which suggests that most of PRL’s target tissues are modulated rather than dependent on PRL.

• The significance of PRL can be seen in the inhibition of lactogenesis using bromocriptine and other dopamine analogues, which are PRL inhibitors.

• Oxytocin

• The other important hormone involved in the milk ejection or letdown reflex is oxytocin. When the neonate is placed at the breast and begins suckling, oxytocin is released. The suckling infant stimulates the touch receptors that are densely located around the nipple and areola. The tactile sensations create impulses that, in turn, activate the dorsal root ganglia via the intercostals nerves (4, 5, 6). These impulses ascend the spinal cord, creating an afferent neuronal pathway to both the paraventricular nuclei of the hypothalamus where oxytocin is synthesized and secreted by the pituitary gland. The stimulation of the nuclei causes the release of oxytocin down the pituitary stalk and into the posterior pituitary gland, where oxytocin is stored.

• The infant’s suckling creates afferent impulses that stimulate the posterior pituitary gland. This releases oxytocin in a pulsatile fashion to adjacent capillaries, traveling to the mammary myoepithelial cell receptors that, in turn, stimulate the cells to contract. Oxytocin causes the contraction of the myoepithelial cells that line the ducts of the breast. These smooth muscle–like cells, when stimulated, expel milk from alveoli into ducts and subareolar sinuses that empty through a nipple pore.

• Milk secretion directly correlates with synthesis

• The regulation of milk synthesis is quite efficient. Milk synthesis remains remarkably constant at approximately 800 mL/d. However, the actual volume of milk secreted may be adjusted to the requirement of the infant by feedback inhibitor of lactation, a local factor secreted into the milk; therefore, the rate of milk synthesis is related to the degree of breast emptiness or fullness. The emptier breast produces milk faster than the fuller one.

• Milk production is responsive to maternal states of well-being. Thus, stress and fatigue adversely affect a woman’s milk supply. The mechanism for this effect is the down-regulation of milk synthesis with increased levels of dopamine, norepinephrine, or both, which inhibit PRL synthesis. Relaxation is key for successful lactation.

Biochemistry of human milk

Human milk is a unique, species-specific, complex nutritive fluid with immunologic and growth-promoting properties. This unique fluid actually evolves to meet the changing needs of the baby during growth and maturation. Milk synthesis and secretion by the mammary gland involve numerous cellular pathways and processes (summarized in the table below).

 

The pathways for milk secretion and synthesis by the mammary epithelial cell. I: Exocytosis of milk protein, lactose, and other components of the aqueous phase in Golgi-derived secretory vesicles. II: Milk fat secretion via the milk fat globule. III: Direct movement of monovalent ions, water, and glucose across the apical membrane of the cell. IV: Transcytosis of components of the interstitial space. V: The paracellular pathway for plasma components and leukocytes. Pathway V is open only during pregnancy, involution, and in inflammatory states such as mastitis. SV = Secretory vesicle; RER = Rough endoplasmic reticulum; BM = Basement membrane; MFG = Milk fat globule; CLD = Cytoplasmic lipid droplet; N = Nucleus; PC = Plasma cell; FDA = Fat-depleted adipocyte; TJ = Tight junction; GJ = Gap junction; D = Desmosome; ME = Myoepithelial cell.

The processing and packaging of nutrients within human milk changes over time as the recipient infant matures. For example, early milk or colostrum has lower concentrations of fat than mature milk but higher concentrations of protein and minerals (see the image below). This relationship reverses as the infant matures.

Lactose, protein, and total lipid concentrations in human milk.

Important biochemical points are discussed below.

• Fore and hind milk (important differences)

• In addition to the changes from colostrum to mature milk that mirror the needs of the developing neonate, variation exists within a given breastfeeding session. The milk first ingested by the infant (fore milk) has a lower fat content. As the infant continues to breastfeed over the next several minutes, the fat content increases. This hind milk is thought to facilitate satiety in the infant. Finally, the diurnal variations in breast milk reflect maternal diet and daily hormonal fluctuations.

• Specific enzymes to aid neonatal digestion

• Human milk contains various enzymes; some are specific for the biosynthesis of milk in the mammary gland (eg, lactose synthetase, fatty acid synthetase, thioesterase), whereas others are specific for the digestion of proteins, fats, and carbohydrates that facilitate the infant’s ability to break down food and to absorb human milk. Certain enzymes also serve as transport moieties for other substances, such as zinc, selenium, and magnesium.

• Three-dimensional structure of human milk

• Under a microscope, the appearance of human milk is truly amazing. Although it is a fluid, human milk has substantial structure in the form of compartmentation. Nutrients and bioactive substances are sequestered within the various compartments of human milk. The most elegant example of this structure involves lipids. Lipids are enveloped at the time of secretion from the apical mammary epithelial cell within its plasma membrane, becoming the milk-fat globule. Certain proteins, growth factors, and vitamins also become sequestered within this milk-fat globule and are embedded within the membrane itself.

• The membrane acts as a stabilizing interface between the aqueous milk components and compartmentalized fat. This interface allows controlled release of the lipolysis products and transfer of polar materials into milk serum (aqueous phase). The bipolar characteristics of the membrane are also necessary for the emulsion stability of the globules themselves; thus, the structure of human milk provides readily available fatty acids and cholesterol for micellar absorption in the small intestine.

• Proteins, carbohydrates, and designer fats for optimal brain development

• Human milk provides appropriate amounts of proteins (primarily alpha-lactalbumin and whey), carbohydrates (lactose), minerals, vitamins, and fats for the growing term infant. The fats are composed of cholesterol, triglycerides, short-chain fatty acids, and long-chain polyunsaturated (LCP) fatty acids. The LCP fatty acids (18- to 22-carbon length) are needed for brain and retinal development. Large amounts of omega-6 and omega-3 LCP fatty acids, predominately the 20-carbon arachidonic acid (AA) and the 22-carbon docosahexaenoic acids (DHAs), are deposited in the developing brain and retina during prenatal and early postnatal growth.

• An infant, particularly a preterm infant, may have a limited ability to synthesize optimal levels of AA and DHA from linoleic and linolenic acid. Therefore, these 2 fatty acids may be considered essential fatty acids.

• Many infant formulas in the United States have added AA, DHA, or both. The amount of AA and DHA in breast milk varies with the maternal diet.^{[1, 9]} The unique blend of fatty acids in the breast milk has been linked to the development of innate and adaptive immune regulation.

• Prior to routine fortification of formulas with DHA and AA, infants who received breast milk demonstrated better visual acuity at age 4 months and slightly enhanced cognitive development than formula-fed infants. This has not been a universal finding, and some have continued to doubt the benefits of DHA and ARA.

• However, in a most recent study of children at age 5 years who were breastfed and whose mothers were given a modest DHA supplement until 4 months postpartum, there was a significant improvement in sustained attention when compared to children whose mothers were not given DHA.^[10]

• A recent study compared growth and bone mineralization in very low birth weight infants fed preterm formula with those who received term formula; the conclusion was that preterm formula better aided in growth and development.^[11]

• One study examined maternal dietary manipulation of fatty acid concentration and neurodevelopmental differences in human milk.^[12] Despite higher levels of AA and DHA in the heavily supplemented maternal groups, no differences were observed in the neurodevelopmental outcomes of the 3 groups. This finding supports a more global effect of human milk as opposed to a single agent that renders developmental differences.

• Thus, whether healthy term infants benefit from the addition of DHA and AA to formula remains unclear because they are able to convert very LCP fatty acids to DHA and AA. Ill term infants and those born prematurely are most likely to benefit from formulas enriched with DHA, AA, or both.

• Rather than producing better vision or greater intelligence, breast milk may somehow protect the developing neonatal brain from injury or less optimal development by providing necessary building materials and growth factors that act synergistically rather than in isolation.

Immunologic properties of human milk

Through the years, knowledge about the immune properties and effects of human milk has grown. A recommended comprehensive review by one of the pioneers in the field, Dr. Armand Goldman, appeared in Breastfeeding Medicine (2007).^[13] Below are the highlights of just some of many known immune properties and functions of human milk.

• Human milk immunoglobulins

• Human milk contains all of the different antibodies (M, A, D, G, E), but secretory immunoglobulin A (sIgA) is the most abundant. Milk-derived sIgA is a significant source of passively acquired immunity for the infant during the weeks before the endogenous production of sIgA occurs. During this time of reduced neonatal gut immune function, the infant has limited defense against ingested pathogens. Therefore, sIgA is an important protective factor against infection.

• Assuming that the mother and her infant, who are closely associated, share common flora, the antigenic specificity of the mother’s sIgA in her milk is directed against the same antigens in the neonate. Maternal immunoglobulin A (IgA) antibodies derived from the gut and respiratory immune surveillance systems are transported via blood and lymphatic circulations to the mammary gland, ultimately to be extruded into her milk as sIgA. The packaging of IgA with a secretory component unique to the mammary gland protects the sIgA from stomach acids, allowing it to reach the small intestine intact.

• Other immunologic properties of human milk

• In addition to antibodies, human milk has numerous factors that can affect the intestinal microflora of the baby. These factors enhance the colonization of some bacteria while inhibiting the colonization by others. The immunologic components include lactoferrin, which binds to iron, thus making it unavailable to pathogenic bacteria; lysozyme, which enhances sIgA bactericidal activity against gram-negative organisms; oligosaccharides, which intercept bacteria and form harmless compounds that the baby excretes; milk lipids, which damage membranes of enveloped viruses; and mucins, which are present on the milk-fat globule membrane. Mucins adhere to bacteria and viruses and help eliminate them from the body. Interferon and fibronectin have antiviral activities and enhance lytic properties of milk leukocytes.

• Our understanding of the interactional effect of these bioactive constituents, the impact of microbiota on gut function, and development (and role of human milk in that development) is just beginning to be understood.^{[14, 15]} These constituents clearly have profound effects of the health status of individuals throughout life, particularly during infancy.

• Human milk leukocytes

• Macrophages comprise 40-60% of the cells in colostrum, with the remainder of cells primarily consisting of lymphocytes and polymorphonucleocytes. Extruded into the milk are rare mammary epithelial cells and the plasma membrane-bound lipid droplets referred to as milk-fat globules. By 7-10 days postpartum, with the transition from colostrum to mature milk, the percentage of macrophages then increases to 80-90% at a concentration of 10⁴ -10⁵ human milk macrophages per milliliter of milk. Milk leukocytes can tolerate extremes in pH, temperature, and osmolality. They have been shown to survive for as long as a week in baboons and lambs.

• Passive immunity from mother to recipient breastfeeding infant

• While awaiting endogenous maturation of the baby’s own immunologic systems, various immunologic and bioactive milk components act synergistically to provide a passive immunologic support system from the mother to her infant in the first days to months after birth. Ingested milk passively immunizes the neonate. Numerous studies have clearly documented this scenario and its clinical benefit, demonstrating decreased risk for gastrointestinal and respiratory infections, particularly during the first year of life.

• Evidence is increasing that these immune and bioactive substances prime the neonatal GI and immune systems in their selective recognition of antigens and development of cellular signaling. This may explain the decreased risk of intestinal and respiratory allergy in children who have been breastfed and the lower-than-predicted risk of autoimmune diseases in the breastfed population. Direct effects are difficult to prove given the multifactorial nature of such diseases; however, when taken together, the data support the beneficial nature of human milk for the developing infant.

Bioactive properties of human milk

Human milk also contains growth modulators, such as epidermal growth factor (EGF), nerve growth factor (NGF), insulinlike growth factors (IGFs), and interleukins. Transforming growth factor (TGF)–alpha, TGF-beta, and granulocyte colony-stimulating factor (G-CSF) are also identified in human milk. These growth modulators are produced either by the epithelial cells of the mammary gland or by activated macrophages, lymphocytes (mainly T cells), or neutrophils in the milk. EGF and TGF-alpha were found at higher concentrations in the milk of mothers who delivered prematurely compared with those who delivered at term. EGF, TGF-alpha, and human milk stimulate fetal small intestinal cell proliferation in vitro, with the greatest increase in cell proliferation seen following exposure to human milk.

Certain bioactive substances and live cells in milk appear to influence neonatal gut maturation and growth through their transfer of developmental information to the newborn. Although most of these biosubstances have been identified in mother’s milk in quantities that exceed maternal serum levels, their exact role in human newborns is uncertain; most current information is from animal models whose development may significantly differ.

Conclusion

Human milk, in addition to its numerous nutrients that make it an ideal food source for the growing term infant, is a bioactive fluid that evolves from colostrum to mature milk as the infant matures. This bioactive fluid contains numerous factors and live cells that, in concert, promote the growth and well-being of the breastfeeding infant. Oliver Wendell Holmes said it best when he stated, “A pair of substantial mammary glands has the advantage over the two hemispheres of the most learned professor’s brain, in the art of compounding a nutritious fluid for infants.” With the ever-expanding knowledge resulting from current research, commercial formula clearly cannot replicate all of the valuable properties that are inherent in human milk.

Calendar of immunization IN UKRAINE

 

Procedures for vaccinations

1. Vaccivations for age

 

 

¹ Vaccinations are subject to all infants who do not have contraindications to this. Vaccination is carried out on the 3-5th day of life (not before 48 o’clock after birth). For the vaccination of premature infants weighing ≥ 2000 g should be used vaccine for tuberculosis with reduced antigen content.

Vaccines for the prevention of tuberculosis not spend one day with other vaccines and other parenteral manipulations.

Children who were not vaccinated in the maternity hospital, subject to mandatory vaccination in health facilities.

If a child is not vaccinated in the maternity hospital because of medical contraindications, vaccination with BCG vaccine-held meters, otherwise vaccinated conducted vaccine for the prevention of tuberculosis (hereinafter – BCG).

Children under the age of two months, vaccination against tuberculosis is made without prior Mantoux test. After two months of age before performing BCG vaccinated child should spend Mantoux test. Vaccination is carried out with a negative result samples.

For the purpose of early detection of TB Mantoux test with the second tuberculin units of tuberculin used for all children 12 months of age regularly once a year regardless of the previous result.

Revaccination against tuberculosis to be children under 7 years of negative Mantoux test. Conducted BCG vaccination.

Due to the fact that preventive vaccination may affect sensitivity to tuberculin during tuberculin age it is necessary to plan for the vaccination. If for whatever reason Mantoux test conducted after the immunization, tuberculin must be made no earlier than one month after vaccination.²

Vaccinations for hepatitis B are subject to all newborns. For the vaccination of children against hepatitis B scheme used: 0 (first day) -1-6 months of life.

  Newborns weighing less than 2000 g born to HBsAg positive mothers, vaccination at birth made sure the scheme 0-1-2-7 (0 – the first day of life, the date of the first injection of the vaccine, the minimum interval between the first and second vaccination – 1 month, the second and third vaccinations – 1 month, third and fourth inoculations – 5 months).

  Features of hepatitis B vaccination of childreot vaccinated by age given in section 2 of this chapter.

 

3 Vaccinations for diphtheria, tetanus and pertussis conducted by age 3 months (first vaccination), 4 months (second vaccination), 5 months (third vaccination) and 18 months (fourth inoculation).

The interval between the first and second, second and third vaccine against diphtheria, tetanus is at least 1 month. The interval between the third and fourth vaccination must be at least 12 months.

 

For the vaccination of children against pertussis in the first year of life can be used as vaccines with acellular (hereinafter – ADTP) and with tsilnoklitynnym (hereinafter – DTP) pertussis component.

The tolerated pertussis in history is not a contraindication for vaccination against the disease.

Vaccination against pertussis is made for children under 6 years 11 months 29 days.

Revaccination against diphtheria and tetanus in 6 years spend toxoid diphtheria-tetanus (hereinafter – ADP) in the next 14 years and in 18 years – diphtheria toxoid-tetanus with reduced antigen content (hereinafter – ADT-M).

The first routine revaccination of adults by age and epidpokazamy that were previously vaccinated, spend ADP-M intervals of 5 years after the last vaccination. Further routine revaccination of adults conducted ADP-M with a minimum interval of 10 years from the previous vaccination ADP-M.

Features vaccination of children against pertussis, diphtheria and tetanus, are not vaccinated by age given in section 2 of this chapter.

 

4 inactivated vaccine against polio (hereinafter – IPV) is used for the first two immunizations, while contraindication to administration of oral polio vaccine (hereinafter – OPV) – all these vaccinations for this Calendar.

OPV vaccine used for 3-6th vaccinations (immunizations by age – 5 months, 18 months, 6 years and 14 years) in the absence of contraindications to OPV.

IPV vaccine can be used for 3-6th vaccinations both separately and in combined vaccines.

Children who are in a family environment with HIV – infected or persons who enter contraindicated OPV, IPV vaccine produced exclusively-vaccine.

Features vaccination of children against polio is not vaccinated by age given in section 2 of this chapter.

After vaccination OPV proposed to restrict injection routine operations within 40 days, avoid contact with individuals whom contraindicated input IPOs. 

⁵ Vaccination of children for the prevention of infection caused by Haemophilus influenzae type rod b (further – Hib-vaccine) may be conducted monovaccines and combination vaccines containing Hib-component. Using Hib-vaccine for primary vaccination should be given preference combination vaccines with Hib-component.

Vaccines for the prevention of infection caused by Haemophilus influenzae type rod b, should be made under the scheme 03/04/18 months.

 

 

 

Vaccination against Hib-infections conducted for children up to 4 years 11 months 29 days.

 

6 Vaccination for the prevention of measles, mumps and rubella performed at age 12 months. Second vaccination – at age 6 years.

Children who have not been vaccinated against measles, mumps or rubella by age of 12 months and 6 years, vaccination can start at any age up to 18 years. In this case, the child should receive 2 doses of compliance with the minimum interval between doses.

Previously ported measles, mumps or rubella is not a contraindication to vaccination.

We should first start the vaccination series, if there was a missed dose, no matter how much time has passed.

 

 

 

¹ According to the instruction on the use of vaccines and / or toxoids.

2 If necessary, the doctor has the right to enter all vaccines, toxoids, as shown by Kalandarem (except BCG) per visit to a health, spending injections in different areas of the body, provided that it is not contrary to the instructions on the application of specific vaccines . Otherwise, the doctor plans the vaccinations given minimum interval between administration of vaccines, toxoids.

 

LIST OF MEDICAL contraindications to preventive vaccinations

 

 

 

1The main criterion for the determination of specific contraindications to vaccine administration is a list of contraindications specified in the instructions for its use.

2. Routine vaccination vaccine, toxoid laid before the acute manifestations of the disease and exacerbation of chronic diseases and are held after recovery or during remission of chronic disease.

3. Immunosuppressive therapy – therapy that is conducted cytotoxic drugs, including cyclosporine A monotherapy and other corticosteroids in immunosuppressive doses of radiation therapy. Immunosuppressive therapy with corticosteroids is recognized if, based on prednisolone is more 1mh/kh/dobu and lasts more than 14 days under conditions of use. Routine vaccination inactivated vaccines and toxoids are held after the end of therapy, vaccination live vaccines not earlier than 1 month after cessation of therapy. If the duration of corticosteroid treatment is less than 14 days, regardless of dose or more than 14 days at a dose prednisolone for less 1mh/kh/dobu or used as replacement therapy, or used topically, such immunosuppressive therapy is not recognized and is not a contraindication for the treatments.

4. After inoculation oral polio vaccine (hereinafter – OPS) proposed to restrict parenteral intervention within 40 days.

5. Vaccination to prevent measles, mumps and rubella after administration of blood products (whole blood, plasma, immunoglobulin preparations, erythrocyte mass) except washed red blood cells is possible in the terms specified in the instructions for use of the drug, but not earlier than 3 months . After emergency prevention of tetanus tetanus human immunoglobulieonatal BCG vaccination is carried out by the conventional scheme. If the interval between vaccination against measles, mumps, rubella and the introduction of drug blood treatment and prevention to less than 14 days, vaccinated against these infections should be repeated.

 

Recommended intervals between vaccination to prevent measles, mumps, rubella and chickenpox, and the introduction of blood products that contain specific antibodies

Drug / indication for the drug	The recommended interval (months)
Emergency immunization Tetanus immunoglobulin human tetanus	3
Passive immunoprophylaxis of hepatitis A normal human immunoglobulin	3
Passive immunoprophylaxis of hepatitis B specific immunoglobulin against hepatitis B	3
Passive immunization of measles normal human immunoglobulin standard contact (without immunodeficiency) immunocompromised	5 6
Transfusion of blood; washed red blood cells; erythrocytes with added preservative (adenine saline); Whole blood (Ht 65%); Whole blood (Ht 35-50%); plasma / platelets	– 6 6 6 7
Immunoglobulin against cytomegalovirus in /v	6
sepsis; thrombocytopenic purpura; Kawasaki disease	8 10 11