RISK FACTORS FOR ANEMIA IN PREMATURE INFANTS 0-12 MONTHS IN MBAGATHI COUNTY REFERRAL HOSPITAL  KENYA

KITHIKII MARY MULI

A90/4602/2017

A PROPOSAL SUBMITTED IN PARTIAL FULFILMENT FOR THE AWARD OF BACHELOR OF SCIENCE DEGREE IN FOOD NUTRITION AND DIETETICS IN THE UNIVERSITY OF NAIROBI

DECEMBER 2019

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1. I understand what Plagiarism is and I am aware of the University’s policy in this regard
2. I declare that this research proposal is my original work and has not been submitted elsewhere for examination. Where other people’s work, or my own work has been used, this has properly been acknowledged and referenced in accordance with the University of Nairobi’s requirements.
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I hereby declare that this report is my own original work and not a duplication of similar published work of any scholar for academic purpose as partial requirement of any college or any other institution of higher learning

Principal Investigator

Mary Muli Kithikii,

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University Supervisor.

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ACKNOWLEDGEMENT

My sincere gratitude to the Almighty for the gift of life and health. Many thanks to my supervisor for guiding me through every step of my project work. Regards to the Department of Food Science, Nutrition and Technology for equipping me with the necessary knowledge needed for the conduction of this research work. Kind regards to my family for the emotional and financial support and lastly I’d like to thank the Mbagathi County Referral Hospital for permitting me to carry out my research there and for the mother child pairs for their voluntary participation.

Table of Contents

Declaration Form for Students. ii

ABBREVIATIONS. v

OPERATIONAL DEFINITIONS. v

INTRODUCTION.. 1

CHAPTER ONE: THE PROPOSAL.. 1

1.1 Background of the Study. 1

1.2      Statement of the problem.. 2

1.3      Justification of the Study. 3

1.3.1       Justification. 3

1.3.2       Beneficiaries of the study. 3

1.5      Purpose of the Study. 4

1.6      Objectives of the Study. 4

1.6.2       General objective. 4

1.6.1.1 Specific objectives. 5

1.7      Hypothesis. 5

1.8      Limitations. 5

CHAPTER TWO: LITERATURE REVIEW… 6

2.1 TOPIC OVERVIEW… 6

2.2 Technical Aspect 7

2.2.1       Inadequate Red blood cell production. 7

2.2.2       Shortened RBC lifespan or hemolysis. 7

2.2.3       Blood loss. 7

2.2.4 Epidemiology. 8

2.2.5 Prognosis. 8

2.2.6 Symptoms of AOP. 8

2.2.7 Medication summary. 8

2.2.8 Maternal Age. 9

2.2.9 Maternal HB and dietary intake. 9

2.2.10 Consequences of anaemia in infants. 9

2.3 Methodology. 10

2.4 Summary of Gaps. 12

CHAPTER THREE: RESEARCH DESIGN AND METHODOLOGY.. 13

3.1 Study Setting. 13

3.1.1 Geographical 13

3.1.2 Topography. 13

3.1.3 Infrastructure. 14

3.1.4 Political Context 14

3.1.5 Demography. 14

3.16 Social Economic Context 15

(Income, Employment, Livelihood, Food security) 15

3.1.7 Agriculture. 15

3.1.8 Health. 15

3.19 Nutrition and Food Safety. 16

3.2 Study Design. 16

3.3 Study Population. 16

3.3.1 Inclusion Criteria. 16

3.3.2 Exclusion Criteria. 16

3.4 Sampling. 16

3.4.1 Sample size determination. 16

[3.4.2 Sampling procedure. 17

3.5 Socio-demographic and economic characteristics. 18

3.5.1Data collection methods. 18

3.5.2 Research tools. 18

3.5.2.2 Equipment 18

3.6 Characterization of Iron deficiency and Megaloblastic Anemia in the chosen sample. 18

3.6.1. Data collection. 18

3.6.2 Research tools. 19

3.6.2.1 Equipment 19

3.7 Adherence to supplementation pre-post natal 19

3.7.1 Data collection method. 19

3.8 Feeding patterns of 6-12 month-year-olds. 19

3.8.1 Data collection method. 19

3.9   DATA QUALITY ASSURANCE.. 20

3.9.1 Recruitment and Training Research Assistants. 20

3.9.2 Pretesting of Questionnaires. 20

REFERENCE LIST. 21

ABBREVIATIONS

AOP – Anemia of prematurity

ANC – Antenatal Care

CI – Confidence Interval

EPO- Erythropoietin

HB- Hemoglobin

IFAS- Iron and Folic Acid Supplement

GOK – Government of Kenya

MOH – Ministry of Health

RBC – Red blood cell

SPSS – Statistical Package for the Social Sciences

SD – Standard Deviation

TB- Tuberculosis

WHO – World Health Organization

OPERATIONAL DEFINITIONS

Prevalence: statistical concept referring to the number of cases of a disease that are present in a particular population at a given time

Preterm: born after pregnancy significantly shorter than normal, especially after no more than 37 weeks of pregnancy

Anaemia: a condition that develops when the blood lacks enough healthy red blood cells or haemoglobin

Normocytic: blood problem where one has normal sized red blood cells, but a low number of them.

Normochromic: a form of anaemia in which the concentration of haemoglobin in the red blood cells is within normal range, but there is an insufficient number of red blood cells.

Hyporegenerative: reticulocyte (immature red blood cell) count of less than 50×109/L

Anaemia of Prematurity: Normocytic, normochromic, hyporegenerative anemia characterized by low serum EPO level

Erythropoietin (EPO): a hormone produced primarily by the kidneys responsible for the production of red blood cells.

CHAPTER ONE

INTRODUCTION

Anemia is a major medical problem affecting children and adults globally. JE LAWN et al. (2013) defines babies born before the 37^th week of gestation as premature. The risk of complications increases the earlier the baby is born. Preterms will often suffer from anemia, immature lungs leading to respiratory distress syndrome, transient tachypnea causing rapid shallow breathing, pneumonia and bradycardia; intraventricular haemorrhage; inability to maintain body heat; juvenile gastrointestinal and digestive system(American Pregnancy Association, 2015)

Maakaron et al. (2018) define anaemia as a condition characterized by a decrease in red blood cell mass.

All infants experience a decrease in haemoglobin concentration after birth. The change from a relatively oxygen deficient state within the uterus to a relatively oxygen suffiicient state with increased tissue oxygenation after delivery leads to an attenuation in erythropoietin (EPO) concentration. For the term infant, physiologic and usually asymptomatic anaemia is observed 8-12 weeks after birth

. It spontaneously resolves in many premature infants within 3-6 months of birth. In others, however, medical intervention is required. Cassady G, Anemia of Prematurity, Rosenkrantz (ed) (Jan 08, 2016)

1.1 Background of the Study

Anemia of prematurity has long commanded the attention of pediatricians who are properly equipped with the physiology and pathophysiology of the condition but not so much the effectiveness of therapeutic methods needed to prevent its prevalence among the preterms to whom there is no resolve at 3-6 months of birth. Cassady G, Anemia of Prematurity, Rosenkrantz (ed) (Jan 08, 2016)

Studies have shown that nutritional deficiencies of iron, folate, vitaminB12, and vitamin E exaggerate the degree of the condition and that inadequate red blood cell production, shortened red blood cell span and blood loss during procedures aimed at correcting some of the complications associated with premature birth could be the cause of the AOP.

According to research, all infants undergo a gradual decrease in hemoglobin levels which elicits a response from the body to increase erythropoietin production but this response is diminished in preterms. The reason for this diminished response is not fully understood but Strauss (n.d.) states that it results from rapid rate of growth and the need for increase in RBC mass to accompany the increase in blood volume, and in sick preterms, from phlebotomy blood losses. Healthy infants barely fall below 9 g/dl at 10-12 weeks while in premature infants, even in those without complications the HB falls to 8g/dl in 1.0-1.5 kgs birth weight and 7g/dl in infants less than 1.0kgs.

Proper prenatal care through consumption of a healthy, balanced diet with plenty of fruits and vegetables and IFAS supplementation could prevent birth of preterms, more so preterms with anemia of prematurity and optimization of the babies nutrition can help reduce the severity of the anemia in preterms.

• Statement of the problem

Anemia is a global health issue affecting most developing countries. Demographic information and food consumption data are being collected using standardized questionnaires by World Health Organization (WHO) for children aged 6-59 months. 15% of low birth weight preterms have anemia at 2 months of age with 50% of blood transfusions to extreme low birth weight infants occurring within the first two weeks when the infants are most sick and blood testing intense. In Kenya 134,000 babies are born before term each year; with 12 number of preterm births per 100 live births placing the county 51 globally. There is a 13 times death risk for preterm babies compared to full term babies (Mutisya J, 17/11/2018). The prevalence of preterm births in Kenyatta National Hospital is 18.3%. Iron and folate prophylaxis are in place, yet despite this, 55% of blood transfusions in the hospital occur in infants aged two months and below. (Wagura, P., Wasunna, A., Laving, A., & Wamalwa, D. (2018). Maternal Hb and age, poor nutritional status, lack of adherence to supplementation among others, all contribute to these preterm births. No studies have been conducted in the Mbagathi County Referral Hospital investigating the prevalence of iron deficiency and megaloblastic anemia despite the infants in Mbagathi hospital receiving both iron and folate Prophylaxis.

• Justification of the Study
  • Justification

Anemia of prematurity is a problem affecting all infants born prematurely. It is expected to resolve at 3-6months after birth and if not, medical intervention employed. It also, has been noted that nutritional deficiencies could exaggerate the degree of the condition, so the infants are supplemented with iron and folate as early as possible. Nutrition plays a crucial role in this as a mother’s poor diet during pregnancy, particularly low in iron, vitamin B₆ and B₁₂ could lead to birth of premature infants.  Anemia is a wide topic and so the need for the existence of research on both iron deficiency anemia and megaloblastic anemia to exist is crucial. This research will investigate this and the risks factors encompassing premature births. Results from this will add to the existing information for policy makers to strengthen interventions addressing preterm births and anemia in infants.

• Beneficiaries of the study.

Table 1, Beneficiaries of the study

• Aim of the study

This study aims to contribute towards research being done on the anemia of prematurity and its risk factors in order to generate data that will lead interventions that reduce its prevalence.

• Purpose of the Study

Purpose of this study is to generate data that can be used by the health care system to address the rates of anaemia among preterms and strengthen interventions in place.

• Objectives of the Study
  • General objective

To assess the risk factors of anemia in infants born prematurely 0-12 months

1.6.1.1 Specific objectives

To determine the socio demographic and socio-economic characteristics of the care givers to the preterms

To assess the adherence to IFAS supplementation pre and post-natal

To characterize iron deficiency and megaloblastic anemia in the preterms aged 0-12months

To assess the feeding patterns of the preterms 0-12 months

• Hypothesis

There is no significant difference in anemia status of preterms meeting their recommended daily iron intake and those not

1.7 Assumptions

It is my assumption that the information I obtain from the patient files rely on what the attending clinicians have recorded.

I assume that the biochemical test results indicate correctly the blood iron levels and complete blood count of the individual subjects.

• Limitations

Delayed lab analysis reports

Missing patient files

Delayed attainment of Ethical Clearance

CHAPTER TWO: LITERATURE REVIEW

2.1 TOPIC OVERVIEW

The strongly marked decrease in hemoglobin concentrations that occurs in extremely low birth weight infants is usually associated with abnormal clinical signs and requires red blood cell transfusion. According to the UK serious Hazards of Transfusion (SHOT) National Haemovigilance Scheme, an increased number of adverse events related to red blood cell transfusion occur in children compared to adults (International Journal of Pediatrics and Adolescents Medicine, 2015)

Dyness Kejo, Pammla M Petrucka, […] , & Theobald CE Mosha conducted a study on prevalence of anemia and its predictors among children under 5 years of age in Arusha District, Tanzania.. 436 children aged 6-59 months were employed and their anemia status assessed by measuring hemoglobin concentration. Demographic information and dietary intake data were collected using a standardized questionnaire WHO for children aged 6-59 months.

Logistic regression using backward procedure was used to estimate odds rations (OR) at 95% confidence intervals (CIs)

Prevalence rate of anemia among under fives was found to be 84.6% (n=369)

Multivitamin logistic regression identified the following predictors of anemia; low birth weight adjusted or (AOR). It was concluded that low birth weight and dietary factors i.e. low or non-consumption of iron-rich foods like meat, vegetables and fruits were predictors of anemia among under five children.

Globally, data indicates that 43% of under 5 children were anemic with prevalence in the developing world, specifically South Asia and East Africa, being 58% and 55%, respectively.

A number of reports suggested rated ranging between 71% and 79% in Kenya, South Africa and Tanzania.

2.2 Technical Aspect

There are three main mechanisms known for development of Anemia of Prematurity

• Inadequate Red blood cell production

Location of RBC and EPO production changes during development. EPO is initially produced in the liver of the fetus and later on in the kidney as development progresses. Towards the end of gestation, it is the liver that is primarily the organ responsible for EPO production. Erythrocytes are synthesized in the yolk sac during the first few weeks of embryogenesis. Towards the end of the first trimester, the liver becomes the primary site of erythropoiesis. At 32 weeks, erythrocyte production is done by the liver and bone marrow equally. At 40 weeks. The bone marrow single-handedly becomes the solo erythroid organ. Premature birth does not fasten the ontogeny of these processes. EPO, whether produced by the body system of administered, has a larger volume of distribution and is more rapidly eliminated by neonates, resulting in a curtailed time for bone marrow stimulation.

Erythroid progenitors in premature infants are quite responsive to EPO, but the response may be blunted if iron or other substrates or co-factors stores are insufficient. While the infant may respond appropriately to increased EPO concentrations with increased reticulocyte counts, rapid growth may prevent the appropriate increase in hemoglobin concentration. (Cassady G, Anemia of Prematurity, Rosenkrantz (ed) (Jan 08, 2016)

• Shortened RBC lifespan or hemolysis.

Cells of the most prematurely born infants only survive 35-50 days due to reduced levels of intracellular adenosine triphosphate (ATP), carnitine, and enzyme activity; increased susceptibility to lipid peroxidation; and increased susceptibility of the cell membrane to fragmentation (Cassady G, Anemia of Prematurity, Rosenkrantz (ed) (Jan 08, 2016)

• Blood loss

Blood samples needed for numerous tests account for 5-10% of total blood losses. (Cassady G, Anemia of Prematurity, Rosenkrantz (ed) (Jan 08, 2016)

2.2.4 Epidemiology

Risk of AOP is inversely related to gestational maturity and birth weight. Half of infants of less than 32 weeks develop AOP. (Cassady G, Anemia of Prematurity, Rosenkrantz (ed) (Jan 08, 2016)

2.2.5 Prognosis

Resolve of AOP is most likely to occur 3-6 months after birth, but this is not always the case. (Cassady G, Anemia of Prematurity, Rosenkrantz (ed) (Jan 08, 2016)

2.2.6 Symptoms of AOP

Poor weight gain despite adequate caloric intake

Cardiorespiratory symptoms i.e. tachycardia, tachypnea and flow murmurs

Decreased activity, lethargy and difficulty in oral feeding

Pallor

Increase in apneic and bradycardic episodes, and worsened periodic breathing

Metabolic academia- increased lactic acid secondary to increased cellular anaerobic metabolism in relatively hypoxic tissues (Cassady G, Anemia of Prematurity, Rosenkrantz (ed) (Jan 08, 2016)

2.2.7 Medication summary

Drugs used to treat AOP stimulate erythropoiesis and provide nutritional substrate needs. Ferrous sulfate/ iron dextran, vitamin E, and Folic acid, along with epoetin alfa, which stimulates RBC production are given.

Ferrous sulfate/ iron dextran (IV) – used in treatment of iron deficiency anemia

Vitamin E- protects polyunsaturated fatty acids in membranes from attack by free radicals and protects RBCs against hemolysis

Folic Acid (Folacin-800) – Water- soluble vitamin used in nucleic acid synthesis. Required for normal erythropoiesis and is an important co-factor for enzymes used in production of RBCs (George Cassady, 2016)

2.2.8 Maternal Age

Older maternal age (˃40) is associated with gestational diabetes, chronic hypertension, obesity and this predisposes them to premature births. Teen mothers (14-17) are also known to be at a higher risk of preterm births as they are most likely to be underweight.

2.2.9 Maternal HB and dietary intake

Maternal anemia during pregnancy is an independent risk factor for low birth weight and before term delivery

Poor nutrition, parasitic and bacterial infection can cause depletion of iron stores in most vulnerable groups, like pregnant mothers, children usually 6-24 months.

Anemia in pregnant women (<11g/dl hb and 33% l  hematocrit) increases effects of maternal blood loss and infections at childbirth and has been linked with maternal and perinatal mortality and morbidity. Now, a dose of 60 mg of iron 400 µg of folic acid daily for 6 months is required to meet the physiologic requirements for iron during pregnancy. Poor adherence hinders women from meeting their body iron requirements and so other interventions have been put in place to prevent and correct iron-deficiency anemia and these include: food fortification, healthy dietary education and anti-parasitic education. The effectiveness of these interventions is still unclear as they also depend on cooperation from the mothers. Consumption of phenolic compound, tannins and phytates present in foods reduces iron absorption in the body.

Research shows that anaemic women are more likely to give birth to premature babies who are also anaemic! Haram, K., Nilsen, S. T., & Ulvik, R. J. (2001

2.2.10 Consequences of anemia in infants

Infants who become anemic may suffer permanent impairment of cognitive development. Anemia in young children has been known to bring about cognitive test scores 12 with IQ tests showing a loss of 10–15 points. The effects do not improve when the anemia is corrected or in later years (Grantham-McGregor, 2001). Another important consequence of iron deficiency is an apparent increased risk of heavy-metal poisoning in children. Iron-deficient individuals have an increased absorption capacity that is not specific to iron. Absorption of other divalent heavy metals, including toxic metals such as lead and cadmium, is also increased. Prevention of iron deficiency, therefore, reduces the number of children susceptible to lead poisoning and boosts their immune system (Abalkhail, 2002).

2.3 Methodology

Previous research on the matter has analyzed maternal variables such as parity, maternal age, number of prenatal visits, family history of smoking and alcohol and drug addiction during study.

Follow-up data on feeding at 6-12 months during the first year of life, Anthropometric parameters, zinc sulphate use and results of routine tests performed at 1 year of correction age (complete blood count, transferrin saturation and ferritin) have also been used to gather the already generated data. Cross-sectional study of randomly sampled cohort infants born before completing 37weeks of gestation more than 14 days in the New Born Unit at Kenyatta National Hospital has been done. Clinical details and biographers have been collected by a predesigned questionnaire. Aseptic micro-sampling techniques have been employed to collect blood in the infants who have satisfied the inclusion criteria. Biochemical tests

These were crucial as they indicated the rates of iron deficiency anemia and megaloblastic anemia as follows:

Hemoglobin determination

A drop of capillary blood is collected by venipuncture from each infants toe/finger prick by a lab technician using a BD contact activated lancets (BD Microtainer). Micro curvets are used to collect the blood sample which is inserted into the Haemcue Hb analyzer and the Hemoglobin level read and recorded. Infants found to be moderately anemic have been referred to the nutrition clinic for further assessments and counseling of the mother as well a close monitoring done while those reported to be severely anemic have been referred to the pediatric department for further medical procedures.  Khusun, H., Yip, R., Schultink, W., & Dillon, D. H. (1999)

Table 2, hemoglobin cut-off points

Folate deficiency determination

The diagnosis of megaloblastic anemia has been made on the basis of the blood count, the findings of macrocytes and hypersegmented polymorphs in the peripheral blood films, and of megaloblastic changes in the bone marrow films. Folate deficiency is established as the cause of anemia by assay of serum and red blood cell folate, and by showing that the anemia responds to folic acid in a physiological dose e.g. 50 μg daily. World Health Organization. (2015

Table 3, Folate concentrations in serum and red blood cells for determining folate status in all age groups, using macrocytic anemia as a hematological indicator

Quantitative data analysis and computation has also been carried out by use of SPSS Version Software

2.4 Summary of Gaps

Only few studies investigate frequency of megaloblastic deficiency anemia despite the infants receiving both iron and folate prophylaxis.

They mostly focus on 6-59 year olds and 2 month old prematurely born infants. What about 0, 3-5 month year olds?

CHAPTER THREE: RESEARCH DESIGN AND METHODOLOGY

3.1 Study Setting

3.1.1 Geographical

Map 1: Location of Nairobi County in Kenya

The study was conducted in Mbagathi County Referral Hospital located in Kenyatta/Golf Course, Dagoretti Division of Nairobi West District. The hospital boarders the Kenyatta National Hospital, Kenyatta City Council Market, Forces Memorial Hospiatl. The Kenya medical Research Institute and the Kibera slums (About Mbagathi County Hospital n.d.)

3.1.2 Topography

The Nairobi County on which Mbagathi hospital is situated is at 1600 to 1800m above sea level, it enjoys tolerable temperatures year round (CBS 2001, Mitullah 2003). The western part of the city is the highest, with a rugged topography, while the eastern side is lower and generally flat. The Nairobi, Ngong and Mathare rivers traverse numerous neighborhoods and the indigenous Karura forest still spreads over parts of Northern Nairobi. The Ngong hills are close by in the east, Mount Kenya arises further in the north, and Mount Kilimanjaro emerges on the plains in Tanzania to the south-east. Minor earthquakes and tremors occasionally shake the city since Nairobi sits next to the Rift Valley, because of the movement of the tectonic plates (Tibaijuki, 2007)

3.1.3 Infrastructure

Nairobi County is taxed with the responsibility of providing a variety of services to residents within its area jurisdiction. These include services that were hitherto provided by the defunct county such as physical planning, public health, social services and housing, Primary Education Infrastructure, inspectorate services, public works, Environment Management. It also offers services transferred from the national government and these include Agriculture, Livestock, Development and Fisheries, Trade, Industrialization, Corporate development, Tourism and Wildlife and Public Service management (About Mbgathi County Hospital, nd)

3.1.4 Political Context

According to About Mbagathi County Hospital (n.d), it is the only public health facility within Nairobi that the Ministry of Health relies on to decongest the Kenyatta National Hospital. Therefore, the level of efficiency with which the hospital delivers services to the public is a matter of national importance. KNH performance influences the attainment of the objectives outlined in the second National Health Sector Strategic plan (NHSSP) of 2005 to 2010 as well as the goals of the national long-term plan, Kenya Vision 2030 and Millennium Development plans (Performance Audit Report of the Auditor General, November 2012)

3.1.5 Demography

Last official population of Nairobi County was taken in 2009 and at that time, the population was 3,138,369. The number has since grown to approximately 3.5 million. The city currently sprawls over a surface area of 696 kilometers squared. This region size in combination with the total number of residents bring the current population density of 4,850 residents per square kilometers.

Primary languages are Swahili and English. The region, is however, ethnically diverse with Luos, Luhyas, and Kambas being the major inhabitants. 20% of the population are kikuyus. Asians, Europeans, and Somalis are also residents. A large number of expatriates also live here due to the job opportunities and this has led to the city’s explosive growth (Nairobi Population, 2019)

3.16 Social Economic Context

(Income, Employment, Livelihood, Food security)

Nairobi is home the Nairobi Securities Exchange, one of Africa’s largest exchange and is 4^th in terms of trading volumes and 5^th in Market capitalization. Several of Africa’s largest companies are headquartered in Nairobi; Safaricom, KenGen, Kenya Aiways. The County manufactures clothing, textiles, building materials, processed foods, beverages, and cigarettes. It also, has a large tourist industry, being both a tourist destination and transport hub.

3.1.7 Agriculture

Urban farmers in Nairobi alone contribute 50,000 bags of maize and 15,000 bags of beans annually and up to a quarter million chickens, about 45,000 goats and sheep and 42 million liters of milk (Food Planning and Innovation, nd)

 3.1.8 Health

Preventive, Curative and Protective, Reproductive health services through a network of over 80 health centers and three hospitals spread across the city.

Mama Lucy Kibaki District Hospital, Mbagathi District Hospital, Pumwani Maternity Hospital and Kenyatta National Hospital are the hospitals in the county with several health facilities in Starehe, Kasarani, Kamukunji, Westlands, etc.

Diarrheal diseases, HIV/AIDS & TB, neonatal diseases, other communicable diseases, mental and substance abuse, cardiovascular diseases, unintentional injuries, nutritional deficiencies, neoplasms, and NTDs and malaria are the ten top causes of mortality in the region.

3.19 Nutrition and Food Safety

The state of nutrition and food security is still under scrutiny

3.2 Study Design

A descriptive cross-sectional study design was used in my research

3.3 Study Population

The study population was premature infants/mother or caregiver pairs admitted in or under follow up in Mbagathi County Referral Hospital.

3.3.1 Inclusion Criteria

Prematurely born infants, both male and female between 0-12 months who have or have not been on iron/folate multivitamin or mineral supplements admitted in Mbagathi Hospital

3.3.2 Exclusion Criteria

Prematurely born infants with gestational age >36 weeks, chromosomal abnormalities or genetic syndromes.

3.4 Sampling

3.4.1 Sample size determination

Sample size was determined using the Fischer’s formula

n= (z²*p*q) ÷ d²

Where:

n- Desired sample size

z- The standard normal deviation set at 1.96 of the 95% confidence interval

p- Prevalence of anemia in long-stay preterm infants according to a study done in KNH is 40 %( p= 0.05)

d- The degree of accuracy desired set at 0.05 significance

(1.96² * 0.4 * 0.6)÷ 0.05²

= 368 preterm infants

N˂10,000

n^I=   n—————

[ 1 + n/N ]

Where N is 50

And n is 368 preterm infants

Modified sample = 44 infants

With 10% attrition rate = 50 infants

3.4.2 Sampling procedure

Mbagathi Hospital was conveniently chosen. The pediatric wards, new born unit and the special surgery PICU were segments of the inpatient clinics purposively chosen, as all preterms born or admitted are found in these wards. The outpatient clinic was also purposively chosen, in which the Neonatology outpatient clinic that follows up preterms from home after discharge from the hospital was selected using segmented sampling and the individual subjects from each unit systematically selected randomly.

3.5 Socio demographic and economic characteristics

Maternal age, level of education, number of children and occupations were the variables that were investigated.

3.5.1Data collection methods

Data was collected through administration of pretested structured questionnaires and interviews

3.5.2 Research tools

Pretested Structured Questionnaires

3.5.2.2 Equipment

Pens

3.6 Characterization of Iron deficiency and Megaloblastic Anemia in chosen sample.

Hb levels and Serum and RBC cell folate levels were examined and recorded

Patient files were reviewed for data

3.6.1. Data collection

No blood was drawn. Information was attained from review of lab analysis reports contained in the patient files.

3.6.2 Research tools

3.6.2.1 Equipment

Notebooks

Pens

3.7 Adherence to supplementation pre-post natal

Data was collected from mothers on the adherence to IFAS supplementation while pregnant and to their infants after giving birth. Mother-child clinic books were also reviewed for this information

3.7.1 Data collection method and tools

Conduction of an in-depth interview

A consent form, question guide, recorder, notebooks and pens were used.

3.8 Feeding patterns of 0-12 month year olds

Feeding patterns from birth to when complementation was initiated until present age (at the time of data collection) was assessed.

3.8.1 Data collection method

Information was drawn from conduction of in-depth interviews.

Information was audio-recorded, written-recorded and a flexible interview question guide used by the enumerator to run the interviews.

3.9   DATA QUALITY ASSURANCE

The principal investigator (I) ensured frequent supervision of the research assistants during data collection. Field assistants received proper training prior to data collection to avoid errors in recordings.

The completed questionnaire was cross-checked and examined after pretesting to ensure no important questions were emitted.

It was ensured that all subjects met the inclusion criteria before being selected as samples and all samples randomly selected to avoid biasness.

3.9.1 Recruitment and Training Research Assistants

Three research assistants were recruited all 18 years and above, 2 of them holders of a nutrition diploma while the other one a data analyst. The research assistants were able to speak fluent English and Kiswahili and have basic knowledge on data collection using questionnaires and in-depth interviews. They were trained for 2 days to equip them with knowledge on how to administer and fill questionnaires as well as record and interpret biochemical lab analysis reports.

3.9.2 Pretesting of Questionnaires

Pretesting was carried out at Kangemi Health Center, targeting at least 4 caregivers to infants and the information collected was used to modify questions so as to give the desired results.

3.10 Ethical consideration

The permission to carry out the study was obtained from Mbagathi County Referral Hospital by submitting the research proposal to the hospital’s Ethics and Research Committee. The respondents were given an opportunity to ask questions and decline participation if necessary and all participants signed a consent form. Confidentiality and privacy was maintained and the caregivers assured of this.

Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 23.0.

The Student t, Mann–Whitney, chi-square and Fisher exact tests were used in analysis

CHAPTER FOUR: RESULTS

Introduction

A variety of factors influence the development of anemia in the first years of life. Caretaker’s schooling and occupation number of siblings, food intake, quality of medical care, nutritional status, biological factors such as low birth weight and prematurity are among the factors that play a role in anemia among preterms. This chapter entails presentation of results and a discussion of the research work.

4.1 SOCIO-DEMOGRAPHIC/ECONOMIC FACTORS AND THEIR RELATIONSHIP TO ANEMIA AMONG PRETERMS

Socioeconomic and environmental factors were significantly associated with anemia on bivariate analysis

50 preterm VLBW infants, 46% males and 54% females, with mean birth weight and gestational age of 1185 ± 229 g and 30.4 ± 2.3 weeks, respectively, were included.

Fig 4.11, frequency of the sex of the preterms.

Younger maternal age remained independently associated with anemia in preterm VLBW infants after adjustment for alcohol intake, smoking and maternal education level, and correction of birth weight and gestational age.

50% were aged 18-27 years, 30% were aged between 28 to 37 years, 16% were aged between 38 to 47 years and 4% respondents below 18 years

Figure 4.12, maternal ages of the respondents

Marital status of the respondents

The frequency of respondents who were single was 18%, followed by 70% being married, 6% of them widowed and 6% divorced. This data indicates that majority of the mothers were married, with the least sample number being widowed

Table 4, Marital status

LEVEL OF EDUCATION

40% of the respondents had completed primary school, 30% secondary level, 22% had gone up to the tertiary level of education and 8% of the respondents had no formal education at all. Majority of the respondents were on the primary level of education with the least percentage having no formal education

Figure 4.1.3. Level of education

OCCUPATION

52% of respondents were business owners, 22% were employed, 6% were students and unemployed were 20%. The minority were students under the care of their parents or relatives, while the greater percentage were business owners.

Table 5 Occupational Status

Table 6, Perinatal socio-economic variables according to the presence of anemia at 0-12 in preterms were

Data expressed as mean ± standard deviation or median (interquartile range).

Student t-test, Mann–Whitney U, chi-square test or Fisher exact test were used.

4.2 Pre-natal Clinic Visits and adherence to Supplementation

All preterm infants born at the Mbagathi County Referral Hospital are routinely referred to the Neonatology outpatient clinic for monthly follow-up visits until 6 months of age and every 2 months thereafter until 12 months of age.. Before hospital discharge, preterm VLBW infants are prescribed Folic Acid prophylaxis, Ranferon and vitamin A, C and D (400 IU vitamin D/d) which are continued throughout the first year of life, with dosage adjustments according to weight gain as determined on follow-up visits.

44% of the respondents received ANC services more than 4 times, 36% respondents between 2 to 3 times, 18% attended once and 2% did not remember.

The mothers who managed a 36% of pre-natal clinic visit gave late pregnancy discovery and early labor as reasons for the few number of clinic visits while those at 9% were mostly students who found it difficult to attend the clinic due to stigmatization or just married/widowed/single mothers who found no need for soo many clinic vistis.

Table 7, Number of times ANC care was received.

The overall sample, and subgroups anemic and non- anemics in relation to the variable number of prenatal visits were

Table 8, Medium (interquartile ranges) of anemic and non-anemics as compared to prenatal clinic visits

And this data was expressed as medium (interquartile ranges). Student t test and Fisher exact were used in analysis

The adherence to supplementation differed from the clinic attendance. The 2% respondents who could not remember if they visited the clinic during pregnancy did not take IFAS. 50% completed the dosage given to them while 48% did not complete the dosage.

The respondents gave boosting blood and ensuring sufficient ‘calcium’ stores for the fetus as reasons for the IFAS supplementation. The 50% that completed their dosage reported they found the supplements tasteless or tasty while those that did not complete their dosage gave nausea, finances, early labour and lack of knowledge on the importance of IFAS as reasons for the lack of adherence.

Figure 4.21 Adherence to IFAS supplementation

Neonatal folic acid supplementation variables according to the presence of anemia in the study subjects were

Figure 4.22, Preterm adherence to supplementation

4.3 CHARACTERIZATION OF IRON DEFICIENCY AND MEGALOBASTIC ANEMIA IN THE PREMATURE SUBJECTS

Mean ± standard deviations of the gestational age in weeks was 30.4 ± 2.3 for the overall sample (N=50), 30.7 ± 2.1   for the preterms with anemia (n=15) and     30.2 ± 2.2 for those with no anemia (n=35). Mean ± standard deviation of the birth weights recorded in grams was 1185 ± 229 for the overall sample (N=50), 1216 ± 223 for those with anemia (n=15) and 1174 ± 231 for those without anemia (n=35). This data was analyzed using student test and the Mann-Whitney test

Figure 4.31, birth weight trend of the study subjects

As expected in a high-risk population, 59% of the newborns received packed red blood cell transfusions in the NICU (mean transfused volume, 15 ml/kg) and 68% received Folic Acid and Ranferon for prevention of anemia. Neither strategy was effective at reducing the prevalence of anemia at 12 months of age.

The mean haemoglobin levels at discharge were 10.3 ± 1.5 for the overall population, 9.9 ± 1.4 for the preterms with anemia and 10.3 ± 1.5 those without anemia.

Table 9, Variables of the 12 months’ CA preterm infants, according to the presence of anemia were as follows:

Data expressed as mean ± standard deviation or median (interquartile range).

4.4 Assessment of feeding patterns

Feeding with cow’s milk at 6 months of age was significantly associated with presence of anemia. Preterms breastfeeding at 0-6 months were 47 in total, those of formulae 3 all of which were anemic, those on exclusive breastfeeding 25 and only one was on both breast milk and formulae

Feeding pattern at 6 months of age

Figure 4.41 Feeding patterns 0-6 months in relation to anemia

Table 10, Feeding patterns at 0-6months of age

Feeding patterns at 6-12 months of age indicated a larger fraction of preterms on cow’s milk had anemia, while those on breastfeeding had a lower number of anemic preterms.

Figure 4.42 Feeding pattern at 12 months of age

Complementation

42% of the study subjects were aged 6-12 and on complementary feeding. Out of the 42%, 26% were unable to meet their recommended daily iron intake of 11 milligrams. Of the 26%, 55% were anemic. Descriptive statistics was used and results expressed as mean and standard deviation, level of significance ≤0.05 Increased consumption of cow’s milk at 6 months and the mixing of foods with high levels of oxalates, tannins and phytates contributed to the reduction of iron bioavailability in the body [relative risk (RR) 1.687; 95% CI 1.146–2.483.

This variable, was thus, independently associated with anemia and the hypothesis there is no significant difference in degree of anemia in preterms feeding on iron-rich diets and those on poor iron-rich diets is therefore, rejected.

Discussion

4.1 SOCIO-DEMOGRAPHIC/ECONOMIC FACTORS AND THEIR RELATIONSHIP TO ANEMIA AMONG PRETERMS

There is evidence that socioeconomic status, household income and education level are inversely associated with the number of offspring.

Although higher maternal education level is a marker of healthy choices that influence child feeding patterns, the literature is controversial in terms of the role of maternal education as a risk factor for anemia. In South Korea, maternal education level has been associated with iron deficiency In Brazil, Oliveira et al. found higher prevalence of anemia in children whose mothers had had <4 years of formal schooling. Conversely, Hadler et al. found no influence of maternal education in a sample of children aged 6–12 months. Levy-Costa and Monteiro report that higher maternal education level and higher household income were associated with increased dietary iron density. In a large U.S. study, Looker et al. found higher prevalence of anemia among individuals with <12 years of formal education and from lower social strata. In our study, maternal education was not independently associated with anemia, which shows no relative influence of this factor on the occurrence of anemia in preterm VLBW infants. Younger maternal age and greater number of pregnancies were associated with higher prevalence of anemia, as previously reported  Silva et al. found that infants who had a sibling aged <5 years were at higher risk of anemia, suggesting that a greater number of siblings translates into less attention to the individual child.

There were no differences in gestational age, birth weight, maternal education level or household income observed between the groups.

4.2 Pre-natal Clinic Visits, admissions and adherence to Supplementation

Majority of the respondents did adhere to the pre-natal clinic visits, with 44% receiving ANC services more than 4 times, 36% respondents between 2 to 3 times, 18% attended once and 2% did not remember. Adherence was not, therefore an issues with an exception of the 18% that gave finances and inability to detect early signs of pregnancy as reasons behind failing to attend the clinic.

Ferritin levels are easily affected by the presence of infection, and in my sample, I had a rate of recurrent admissions that was close to 50%, with infection as the leading primary or secondary cause. So, one of the criteria used for diagnosis of iron deficiency was transferrin levels, which, unlike ferritin, is not affected by the presence of infection.

Based on a study by Sherriff et al. investigators in the UK proposed changing the hemoglobin cutoff level for diagnosis of anemia to 10 g/dl—which entailed a decrease in the prevalence of anemia to 7.1% from 22.7% in that specific cohort. Using these revised cutoff values in our sample would reduce the prevalence of megaloblastic anemia to 10.6% (from 26.5%) and increase the prevalence of iron deficiency to 52.3% (from 43.2%). This suggests that, at least for the present sample, the WHO recommendations overestimate anemia and underestimate iron deficiency, an aspect that deserves further investigation. Considering the high-risk nature of the study population and the harmful effects of anemia on child health, I believe that the wider reference ranges of the WHO should be used.

Prophylactic Folic acid and Ranferon supplementation in populations at high risk of anemia, such as preterm VLBW infants, appears to reduce the prevalence of anemia in these groups. In the present study, the prevalence rate of anemia seems to have been checked, at least in part, by adequate monitoring and systematic guidance on relevant aspects, such as Ranferon and Folic Acid prophylaxis, provided as part of outpatient follow-up at the study facility. Nonetheless, younger maternal age, greater number of pregnancies, SGA status and cow’s milk intake at 6 months of age contributed to a higher prevalence of anemia. Implementation of educational strategies focusing on dietary and environmental factors may help reduce the prevalence of anemia in this population.

4.3 CHARACTERIZATION OF IRON DEFICIENCY AAND MEGALOBASTIC ANEMIA IN THE PREMATURE SUBJECTS

In this study, the prevalence of anemia—26.5%—was relatively low as compared with that reported in a systematic review of full-term and preterm infants in Kenya (53%) .This might be explained by the structured follow-up program available to these infants in the hospital, which provided outpatient support after hospital discharge. Furthermore, regular iron and vitamin supplementation are available throughout the first year of life.

Nevertheless, this prevalence was much higher than that reported in developed countries—3–5% in U.S. infants weighing 2000–2500 g at birth to 8% in full-term Canadian infants to 12% in full-term Norwegian infants with a birth weight >2500 g.The fact that we assessed a high-risk subpopulation (preterm VLBW infants) may at least in part explain this difference. However, both the prevalence of anemia (26.5%) in preterms and also in general (48%) in the present sample is a reason for concern. The factors that were independently associated with higher prevalence of anemia were younger maternal age, greater number of pregnancies and SGA status—reflecting a subgroup of preterm infants that is particularly vulnerable to morbidity in the NICU environment and in the first year of life.

The prevalence of anaemia in our sample was low, most likely due to regular Folic Acid and Ranferon supplementation—with control of compliance and iron and Folate administration during follow-up visits—and dietary supervision. Regular iron supplementation is a known strategy for prevention of anemia. A Cochrane review found a significant difference in hemoglobin levels with iron supplementation, but there was no consensus regarding the benefits of supplementation on neurodevelopmental outcomes and growth. In the USA, the use of enriched breakfast cereal and infant formula led to a reduction in iron deficiency and, consequently, anaemia.

Similar to a previous study comparing cord serum ferritin levels at 4 weeks of life in full-term SGA and adequate-for-gestational-age infants , our study found a higher risk of anemia in SGA preterm VLBW infants. Olivares et al. found a lower ferritin concentration in preterm SGA infants at birth as compared with preterm adequate-for-gestational-age and full-term infants, although all preterm infants had low hemoglobin levels at 4 months, even when compared with full-term SGA infants. Karaduman et al. suggested that the low ferritin concentration found in SGA infants results from insufficient placental iron transport or from the characteristically enhanced erythropoiesis in conditions of chronic fetal hypoxia, which is often associated with intrauterine growth restriction.

4.4 Assessment of feeding patterns

I found a significant association between anemia and cow’s milk intake at 6 months of age. An increased prevalence of anemia has previously been described in association with cow’s milk intake before age 12 months in a population of full-term infants. Data from other Kenyan regions show that an increased relative contribution of cow’s milk to feeding is significantly associated with anemia in children <5 years of age. Cow’s milk provides excess protein and minerals, hindering iron absorption. Moreover, its intake is associated with fecal occult blood loss in infants aged <12 months, studies have noted that exclusive breastfeeding until age 6 months is a protective factor against anemia, whereas early introduction of complementary feeding is a risk factor. Sherry et al.  Attributed the continued decline in the prevalence of anemia in the USA to higher breastfeeding rates and iron-enriched formulas. In my study, an association between breastfeeding and decline in the prevalence of anemia was not observed, possibly because of the low breastfeeding rate at 6 months of age in the sample: 17.4% and only 8.3% for exclusive breastfeeding.

Prevalence of anemia in 50 participants was 26.5% [95% confidence interval (CI) 21.8–31.6%] and of iron deficiency was 48% (95% CI 39.0–56.9%).], lower maternal age (RR 0.953; 95% CI 0.923–0.983), high number of pregnancies (RR 1.256; 95% CI 1.122–1.406) and being born small for gestational age (RR 1.578; 95% CI 1.068–2.331) were independently associated with anemia after adjustments.

CONCLUSION

The number of children and maternal age, according to this study contributed to anemia in preterm birth. The mothers feeding habits and adherence to IFAS supplementation during pregnancy were noted to affect the birth of the baby, whether term or preterm.

Follow up after birth, of the child, that ensured iron and folate supplementation and the feeding patterns of the children from day zero to their ages during conduction of the research indicated a significant contribution in the absence or presence of anemia.

RECOMMENDATION

Prevalence of anemia is high during the 1^st year of life of a preterm. Dietary and environmental education strategies may help prevent anemia after discharge.

Mothers should be advised on the importance of ANT clinic visits and IFAS intake during pregnancy. Nutrition education on what is required for feeding especially during the first year of life should be conducted, with emphasis on avoidance of practices that could further contribute to the depletion of the iron stores.

I also recommend that a strict system that ensures that all premature infants are followed up as they continue to grow be instituted in every health care facility that handles them.

Iron-fortified infant formulaes should be encouraged for consumption were breast feeding is impossible.

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APPENDICES

1.0 PARTICIPANT’S STATEMENT.

I Mr/Mrs/Miss……………………………………………aged……………….,acknowledge my understanding of the nature of the study and hereby give consent for myself and my child to participate in it. I am fully aware that I/ my child have the right to withdraw from the research at any time, for any reason, without penalty or harm,

Parent/ Guardian‘s signature ……………………….. Date:…………………………………………..

Mother’s signature on behalf of the child (Assent)………….. Date:…………………………………………..

Researcher/Assistant Signature………………………… Date:…………………………………………..

2.0. In-depth Interview Guide

1) Are you aware that you should be attending Nutrition clinics?

If yes, give reasons,

1. For Nutrition Follow up
2. For growth monitoring
3. For dietary intake monitoring

If no, give reasons

1. Not made aware I should
2. I’m financially unable to
3. My job does not allow me to
4. Not important

2) Is your child on any iron or folate supplements? If yes, for how long now

3) Those whose infants are on complementary feeding

1. a) At what age did you introduce complementary feeding?
2. b) What have you been giving them since you started them on complementation?

4) a)Did you take IFAS during pregnancy? Give reasons for your answer

1. b) Are you aware of what they are used for?

3.0 Questionnaire

Introduction

I am Mary Muli Kithikii, a student of the University of Nairobi conducting a research on anemia in preterms.

The following is a questionnaire that has been designed to obtain information from mothers and caregivers to preterms for purposes of this research. If you wish to participate kindly put your signature below;

Date………………..……………………………………………

Signature……………………………………………………….

Instructions

You are requested to fill all sections (tick or insert the response in the spaces provided) and return it to the enumerator that administers it.

Do not indicate your name. Please note further that your response will be kept confidentially and the findings of the survey used as part of research for academic purpose.

SECTION A: Socio demographic characteristics

1. Sex
2. Female[ ]
3. Male[ ]
4. Relationship with the index child…………………………….

3. Main Occupation
4. Salaried employee[ ]
5. Self-employed[ ]
6. Casual labourer[ ]
7. Student[ ]
8. Unemployed[ ]
9. Relationship to the household head……………………..
10. Level of education
11. Primary[ ]
12. Secondary[ ]
13. Tertiary[ ]
14. None [ ]

SECTION B (Fill in this section if you are the mother to the index child)

6. How old were you when you delivered? …………………………..

7. At how many weeks was the child delivered?……………………

8. Did you attend any clinic visits?
9. Yes [ ]
10. No [   ]

If no, give reasons……………………………………………………………………………………

9. If Yes, When was your earliest clinic visit?
10. 0-16 weeks [ ]
11. 16-28 weeks[ ]
12. 28-32 weeks[ ]
13. 32-40 weeks[ ]

10. How many clinic visits did you attend?
11. 4[ ]
12. 3[ ]
13. 2[ ]
14. 1[ ]
15. None[ ]
16. Were you given any iron supplements?
17. Yes[ ]
18. No [ ]

12. What were the iron supplements for?………………………….

……………………………………………………………………………………..

13. How did you find those supplements?…………………………………………………………..

………………………………………………………………………………………..

14. Did you finish taking them?
15. Yes [ ]
16. No [ ]

15. List down some sources of iron-rich foods

16. Where did you get that information from?………………………………………………………….

…………………………………………………………………………………………….

17. Do you have a history of Anemia both prior to and after pregnancy?
18. Yes [ ]
19. No [ ]

If yes, list some of the symptoms you’ve had

–

–

–

–

17. List down the foods that you majorly consumed during pregnancy

18. How many children do you have?………………………………….

19. Weight gain trend during pregnancy (Referred from the Mother and child health handbook)

Section C (Information of the index child)

20. Name of the index child…………………………….

21. Current age………………………….

22. Birth weight………………………….

23. Current hemoglobin and plasma folate levels…………………..

24. Has……………………………….began complementation?
25. Yes [ ]
26. No [ ]

25. If yes, list down the foods that you started weaning with till current date

Thankyou!

4.0 Enumerator’s agreement form

I……………………………………….agree to participate in the study research involving mother/preterm pairs. I am aware that the data collection period is to last for 5 days, before which I am to attend a training on the various areas required to render me an efficient enumerator.

I understand the importance of professional ethics, and I am willing to oblige. I am also medically covered in the event of harm during data collection.

Signature ……………………………………………………………..

Date……………………………………………………………………..

5.0 Field assistants’ training program

6.0 Focus Group Discussion Question Guide

• How many of you have given birth to, or are taking care of a premature infant?
• At how many weeks was your premature child born?
• How old is he/she now?
• Are you aware that you should be attending Nutrition Clinics?

If Yes, Give reasons,

1. For Nutrition Follow ups
2. For growth monitoring
3. For Dietary Intake monitoring

If No give reasons

1. Not made aware I should
2. I’m not financially able to
3. My job does not allow me to
4. Not important

• Is your child on any iron or folate supplements? If Yes, for how long now
• Those whose infants are on complementary feeding

1. At what age did you introduce complementary foods?
2. What have you been giving them since you started them on complementation?

• a) Have you heard of IFAS?

1. b) Did you take them during pregnancy? Give reasons
2. c) Are you aware of what they are used for?

7.0 RESEARCH BUDGET

8.0 Variables

9.0 Gantt Chart