ORIGINAL

Niger J Paed 2014; 41 (3):209 –214

Ugege MO

Airede KI

Jiya NM

Thyroid function profile in cord

blood and postnatal changes at 24

and 72hours in healthy term

Nigerian neonates

DOI:http://dx.doi.org/10.4314/njp.v41i3,11

Accepted: 25th February 2014

Abstract: Background: Studying

the acute postnatal changes of new-

born thyroid function is essential

for determining the best timing of

screening for congenital hypothy-

roidism. There is paucity of litera-

ture on neonatal thyroid function

and particularly the postnatal

changes in Nigeria.

3

were as follows: T , 0.58 (0.56)

nmol/l, 1.15 (0.77)nmol/l, 0.83

(0.74)nmol/l; T₄, 91 (83.1)nmol/l,

121.5 (106.4)nmol/l, 104.2 (84.2)

nmol/l; and TSH, 5.95 (5.81)mU/l,

8.61 (8.34)mU/l, 2.52 (2.61) mU/

l.. The mean serum T₃_, T₄and TSH

at 24hours were higher than cord

blood levels (p<0.001, 0.03, 0.05

(

)

Ugege MO

Department of Paediatrics,

Usmanu Danfodiyo University

Teaching Hospital, Sokoto.

Email:shallyben@yahoo.com

Airede KI, Jiya NM

Department of Paediatrics,

University of Abuja Teaching Hospital,

Hospital Road, Gwagwalada,

Abuja, Nigeria.

Objectives: To describe the profile

of thyroid function in cord blood

and the postnatal changes at

respectively). The mean serum T

3

and T₄ at 72hours, were higher

than cord blood levels (p = 0.07,

0.44), whereas TSH at 72hours

was significantly lower than cord

blood levels; (p<0.001).

2

4hours and 72hours in healthy

term neonates delivered in Usmanu

Danfodiyo University Teaching

Hospital (UDUTH), Sokoto.

Subjects and methods: This was a

prospective, descriptive and cross

sectional study conducted over a

six month period (between July-

December 2009). Forty seven con-

secutively delivered healthy term

Conclusions: There was a rise,

above cord level, of T₃_, T₄ and

TSH at 24hours, and a decline at

72hours, the latter being most

marked in TSH. It is recommended

that serum TSH taken at or greater

than 72hours of life may be util-

ized for screening for congenital

hypothyroidism in term babies,

using postnatal age appropriate

reference ranges. Serum T₃_, T₄

should then be assayed for confir-

mation in all neonates with a posi-

tive TSH screening.

3 4

neonates had their serum T , T ,

TSH assayed at birth, 24 and

2hours using the Enzyme linked

7

immunosorbent assay (ELISA)

technique. Data obtained are pre-

sented as mean, median and stan-

dard deviation (SD). Paired- t- test

was used for statistical inference.

Results: The mean (SD) of the se-

rum hormone concentrations in

cord blood, and venous blood at

Key words: Thyroid profile, post-

natal changes, Term, Healthy neo-

nates.

2

4hours and 72hours, respectively

2

-4

.

Introduction

development

Thyroid hormones in normal quantities are vital for

physical growth and mental development during fetal

and postnatal life . In the developing human fetus,

Most infants with congenital hypothyroidism are asymp-

tomatic at birth . This may probably be because of an

ectopic thyroid gland with clinically significant thyroid

function, partial defect in thyroid hormone synthesis, or

4

to the moderate amount of maternal T that crosses the

5

1

thyroid hormone deficiency is associated with severe

retardation of growth and maturation of almost all organ

2

systems . However, the sensitivity of different organs to

placenta and is able to boost fetal levels within 25-50%

5

thyroid hormone deficiency varies. The brain is particu-

larly susceptible to damage during the fetal and early

of normal levels at birth . The clinical picture is fully

5

developed by 3 – 6 months of age , by which time ther-

3

postnatal period . It has been established that nerve cells

apy may not prove 100% useful in restoring neurodevel-

6

require thyroid hormone for their development. Thyroid

hormone is therefore, essential for normal brain

opment to normal . Prognosis for neurodevelopment is

excellent if therapy is instituted at the postnatal age of

2

10

7

,8

one month or less. Less than 5% of neonates with con-

genital hypothyroidism are diagnosed clinically first,

delivery rate of approximately 2,500 babies. It also

serves two neighboring states (Zamfara and Kebbi) and

a contiguous neighboring country, Niger Republic.

Sokoto State is located in the Northwestern geopolitical

zone of Nigeria with a population of 3.69million people

5

before laboratory confirmation. The clinician is, there-

fore, dependent on neonatal screening tests for the early

diagnosis. Routine screening is, however, not yet uni-

versal in some countries such as Nigeria, and may be

responsible for the lower prevalence and/or poor docu-

mentation of congenital hypothyroidism in the literature.

7

16

and annual growth rate of 3% . It is situated at 900m

16 0 0

above sea level . It lies between latitude 10 and 14 N,

0

1

0

1

17

and longitude 3 3 N and 7 7 E of the equator . The

climate is semi-arid with a hot dry season that spans

from October to April, a rainy season which starts in

The American Academy of Paediatrics advocates that

blood specimen for screening should be collected opti-

mally by 2-4 days of age , but there are situations in

which this is virtually impossible. In infants discharged

before 48 hours of life following delivery, blood should

be obtained before discharge . In most screening pro-

1

7

May and lasts till September , the cold harmattan

months spanning from December to February. Annual

7

1

7

rainfall ranges between 550mm and 600mm . The tem-

0

perature fluctuates within wide limits from about 15 C

7

0

17

during the cold night to over 40 C during the hot days .

The low ambient temperature during the cold season

grams blood is collected for screening between 5-6 days

of age . Some researchers have documented the use of

9

18

could predispose to higher TSH surge . Most of the

cord blood TSH in term neo_,n₁₀ates as a screening tool for

ethnic groups are represented, but the majorities are the

indigenous Hausas/Fulani population. The society is

basically agrarian with majority living in the rural areas.

Ethical permission to carry out this study was obtained

from the UDUTH Ethics Committee. Informed verbal

and written consent was obtained from the parents of the

babies recruited for the study, during Labour

9

congenital hypothyroidism . They argue that serum

TSH at birth does give reliable and good result. To but-

tress their argument, they opined that the acute changes

take a few hours post-delivery to develop hence it does

not affect cord levels of TSH. Furthermore, the level of

TSH in the cord reflects the concentration of this hor-

mone in the fetus and not early neonatal period that is

fraught with acute changes in TSH levels. Lastly, quan-

tity of TSH in the cord is not affected by maternal levels

Study Design

as compared to T

placenta because of its high molecular weight

4

levels because TSH does no₉t_,₁₀c_,r₁o₁_.ss the

This was a prospective, descriptive and cross sectional

study conducted over a six (6) month period between1st

July 2009 - 31 December 2009.

st

Thyroid profiles have bee₁n₂_,₁₃described in neonates in

Inclusion criteria: These were healthy term neonates,

delivered in UDUTH, Sokoto and informed written pa-

rental consent.

North America and Europe

with the establishment of

reference va₂l_,₁u₃es which are utilized by neonatal screen-

1

ing centers . However, in Africa, limited studies have

Exclusion criteria: They include maternal history/

family history of thyroid₉d_,₂i₀sease or ante-partum inges-

1

4,15

been documented . It was, therefore, considered that

since no study has been done describing thyroid profile

in term neonates in Sokoto, and little is known about its

postnatal changes in Nigerian neonates, particularly in

this part of the country, it was pertinent to undertake this

study. Moreover, studying the thyroid profile of Nige-

rian neonates is a pre-requisite for the establishment of

neonatal screening centers for congenital hypothyroid-

ism in Nigeria.

1

tion of anti-thyroid drugs . Maternal goiter, sick new-

borns₂₁_,(₂b₂ecause of the effect of illness on thyroid func-

21

tion)

, probable sepsis , severe respiratory distress

2

or cardiopulmonary illness , perinatal asphyxi₇a/

2

3

seizures , history of blood transfusion in the neonates.

Recruitment Procedure: The parturient mothers and

some expectant fathers were addressed during labour for

informed/written consent. Forty seven (47) consecutive

babies delivered between 5am and 1pm, who met the

inclusion criteria, were recruited for the study. This spe-

cific delivery time preference was chosen to allow for

uniformity in the time of blood sample collection at

24hours and 72hours, as well as to remove any circadian

bias ( i.e. Circadian rhythm of TSH secretion character-

ized by low concentrations during the daytime, increase

Subjects and Methods

Study location

This study was carried out in the Labour Ward and Spe-

cial Care Baby Unit (SCBU) of UDUTH, Sokoto,

Sokoto State, Nigeria. The SCBU of the hospital adjoins

the Labour ward and admits all babies that are high risk;

this is inclusive of babies with abnormal birth weight,

those who experienced perinatal complications, post

caesarean section and other instrumental deliveries and

sick newborns (the latter are kept in a demarcated sec-

tion of the SCBU).

2

4

in the evening and peak shortly before sleep) .

A thorough physical examination (general and systemic)

was carried out on each neonate after birth and on subse-

quent follow up visits, to ensure they were healthy.

Apgar scores, birth weights, gestational age by dates or

ultrasound, gender, maternal complication (medical or

obstetric), parity and others were documented in the pro-

forma data sheet. The importance and implication of

outcome of the study was further explained to the moth-

ers after delivery. The mothers were also examined for

goiter by palpation of their anterior neck while asking

UDUTH is sited at No. 1 Nadama Road within the

Sokoto Metropolis, the Seat of the Caliphate and the

State capital. It has a 554 bed capacity and an annual

2

11

them to swallow, the investigator standing behind the

mothers during palpation. History of ingestion of anti-

thyroid medication or family history of thyroid disease

was taken and documented in the pro-forma data sheet.

Follow up written appointments were subsequently

given to the mothers to bring their babies at 24hours,

and 72hours. Blood samples were obtained from en-

rolled neonates for the assay of T , T and TSH. Mothers

3 4

were reassured and given incentives for transportation

during follow up visits.

Birth weights and gestational ages of the studied

Neonates

The birth weights of the neonates ranged from 2,150g to

4,900g {mean (SD) 3,230g (2.141)g}. There were thirty

eight (81%), Appropriate for Gestational Age (AGA),

three (6%), Small Gestational Age (SGA), and six

(13%), Large for Gestational Age (LGA) neonates. Ges-

tational ages ranged from 37 to 42 weeks [Mean (SD) 39

(20) weeks]

Blood Sampling: Two milliliters (2mls) of umbilical

venous and arterial mixed blood was obtained by gently

milking a 15-20cm length of the fetal side of the severed

umbilical cord within five minutes of birth of each

baby. Two milliliters (2mls) of venous blood was also

obtained by venipuncture of a peripheral vein at

Mode of delivery

Thirty (64%) of the neonates were delivered via caesar-

ean section (CS), sixteen (34%) by spontaneous vertex

delivery (SVD) and one (2%) by vacuum extraction.

Age, parity and antenatal clinic attendance of mothers:

Forty four (93%) of the mothers were booked and three

(7%) were un-booked. Thirty eight (80%) of the mothers

were multiparous and nine (20%) were primiparous.

Maternal ages ranged from 16 to 39 years. (Mean (SD)

age 26 (14) years).

9

2

4hours, and 72hours using a 21G needle without sy-

ringe, after cleaning the site with a cotton wool wet with

methylated spirit. The blood samples were collected into

a plain sample bottle without anticoagulant and allowed

to clot. It was subsequently spun in a centrifuge at 4000

revolution per minute for five minutes. The serum was

decanted into small tubes using a pipette and kept frozen

0

at -20 C in the freezer of the Chemical Pathology De-

Serum concentrations of T

median serum concentration of serum T

3

, T

4

, and TSH: The mean and

, T , and TSH

partment of UDUTH until required for analysis.

3

4

Blood Analysis Technique: A solid phase enzyme im-

munoassay utilizing the competitive binding principle

in cord blood, at 24hours and 72hours are as shown in

Table 1.Comparison between two means was done

using the paired- t- test. There was a rise above cord

blood levels in all the hormones at 24hours (p = < 0.001,

0.03, 0.05 respectively) and a fall at 72hours (p= 0.05,

0.29, 0.001 respectively), the fall being most marked in

(

thyroxine, and thyroid stimulating hormone . The val-

ELISA) was used for the assay of Triiodothyronine,

25

ues of T3, and TSH were expressed in, ng/dl, µg/dl

T

4

and µIU/ml, respectively. To facilitate comparison with

other studies, these units were converted to their corre-

TSH. At 24 hours, the mean T

3

was about twice the cord

sponding SI units as follows: T

ng/dl×0.01503= nmol/l and TSH µIU/ml= mU/L.

The commercial test kits were obtained from Syntron

Bioresearch, Inc California, USA. The test procedure for

4

µg/dl×12.87=nm₂o₆l/l, T

3

blood value: the mean T level increased by about 30%

of the cord levels while that of TSH increased by about

one and a half times of the cord levels.

4

At 72 hours, the mean T

24-hour levels. However, while the values of T

3

, T

4

and TSH all fell below the

and T

4

triiodothyronine (T

lating hormone (TSH) were as contained in the Syntron

Bioresearch, Inc. Micro well T EIA catalogue 3810-96,

EIA ref #2210-96 and TSH EIA ref #2211-96, re-

spectively.

Data Analysis: The data from pro-forma sheets and

results of serum T , T and TSH were entered into a mi-

3

), thyroxine (T

4

) and thyroid stimu-

3

remained above the cord levels that of TSH fell to about

half the cord value.

3

T

4

Table 1: The mean, standard deviation and the median of se-

rum T , T , and TSH in cord blood of term neonates, and ve-

3 4

nous blood at 24hours and 72hours.

3

4

crocomputer (Microsoft excel 2003). A double check

entry approach was utilized to ensure accuracy of data

entered. Measures of statistical location like mean, stan-

dard deviation, median and range were generated using

the Statistical Package for Social Sciences (SPSS) ver-

sion 20. Statistical comparison involved the paired- t-

test. Probability (p) value less than or equal to 0.05 were

interpreted as statistically significant.

Hormone

Cord blood (CB) 24hrs

72hrs

Mean(SD)

Median

Mean(SD)

Median

Mean(SD)

Median

a

b

c

T₃(nmol/l)

0.58(0.56)

0.45

91.0(83.1)

1.16(0.77)

1.14

0.83(0.74)

0.80

d

e

121.5(106.4) 104(84.2)

f

T

4

(nmol/l)

5

TSH (mu/l) 5.95(5.81)

1.1

81.6

8.61(8.34)

71.6

g

h

i

2.52(2.61)

4

.66

7.08

1.71

CB: C_aord_bblood vs Versu_as

Results

General characteristics of the study population

c

T

3

:

vs

p=<0.001; ^v^s f p=0.05

d

e

d

vs p=0.29

4

_gvs

p=0.03;

p=0.05;

h

g

vs i p=0.001

TSH: vs

Forty seven apparently healthy term neonates were en-

rolled for the study. Eighteen (38%) were males and

twenty nine (62%) were females. (M: F =1:1.61). All

subjects had Apgar scores between 8 and 10 at 1 and 5

minutes, respectively.

Thyroid profile of term AGA neonates in Cord blood

and venous blood at 72hours as seen in this study com-

pared with a similar study in Benin are shown in

Table 2. Similar pattern of a higher mean serum T₃ and

2

12

T

levels was demonstrated.

4

and lower TSH at 72hours compared to cord blood

screening at 72 hours will likely give reliable results

applicable to the neonate in stable state.

4

The neonates in Benin had a lower mean serum T and a

1

5

higher mean serum T

3

and TSH than was demonstrated

A similar study in Benin was conducted in the year

2005 on term AGA neonates. Their serum T , T and

in this study both in cord blood and at 72hours.

3

4

TSH were assayed in cord blood and at

72hours.Comparison with this study, therefore, was only

possible with the term AGA group which were thirty

eight in number. Coincidentally a similar method of

assay was used (ELISA technique₅), though the test kits

.

Table 2: Neonatal thyroid profile of term Appropriate for Gesta-

tional Age (AGA) neonates in Cord blood and venous blood at

2hours in Sokoto (present study) compared with that reported in

Benin (Nigeria)

7

1

Sokoto (Present Study)

Mean (Range)

n=38

Benin Study

Mean (Range)

n=114

were different. The Benin study showed lower mean

4 3

serum T and higher mean serum T and TSH than this

Hormones

present study. This observation may be due to the differ-

ences in location, Sokoto being a mild goiter zone while

Benin is in an area of moderate goiter.

Birth

72hrs

Birth

72hrs

T

3

nmol/L 0.62 (0.01-2.78) 0.83(0.01-3.69) 0.89(0.65-1.52) 1.06(0.71-1.61)

4

nmol/L 91.3 (0.4-265.9) 104(1.0-274.6) 75.48(47-120) 101.38(62.2-130.5)

TSH mU/L 5.89 (0.45-35.76) 2.52(0.04-11.97) 13.59(6.2-26.1) 10.25(5.0-22.1)

Previous work done has shown that newborns from ar-

eas of iodine deficiency as seen in the goiter belts have a

higher frequency of elevated TSH levels and low T

4

values than is found in areas where iodine intake is nor-

mal even though the mothers may be clinically and bio-

Discussion

30

chemically euthyroid . It may be reasonable to proffer

that this would occur more profoundly in areas with

moderate to severe iodine deficiency than the mildly

deficient areas. One of the possible explanations given is

that in the presence of iodine deficiency, the newborn

thyroid is unable to obtain an adequate iodine supply

because of the competition by the mother’s thyroid, also

eager for iodine. This may result in more severe reduc-

tion in the iodine content in the newborn thyroid and

consequently reduction in its functional capacities.The

demonstrated pattern of postnatal changes at 72hours in

The present study has demonstrated higher mean levels

of serum T

pared to cord blood levels of these hormones(<0.001,

.03). This is consistent with the findings of Jacobsen et

3 4

and T at 24 hours in term neonates com-

0

2

7

al in Copenhagen, Denmark.

3 4

The reason for the higher levels of serum T and T at 24

hours is most likely due to adaptive changes in the new-

born, characterized by early rapid increase in serum

TSH in the first few hours of life post-delivery, in all

1

8

groups of newborn . This surge of TSH is called the

physiologic surge, and is as a result of extra-uterine

this study (higher mean T

3 4

, T and lower TSH) com-

18

pared with mean cord blood levels is similar to that re-

cooling . The TSH surge stimulates the thyroid gland to

1

5

18, 28

3 4

increase production of thyroid hormones (T and T )

in order to adapt to extra uterine life via synergistic

ported in Benin . This suggest that the postnatal

changes in neonatal thyroid function are qualitatively the

same irrespective of geographical location but there may

be slight quantitative differences.

action with catecholamine to increase non shivering

thermogenesis. The finding of higher relative increases

of serum T

4, confirms earlier reports that the increased thyroid

hormone secretion following the TSH surge is due more

3

above cord levels, at 24 hours, compared to

1

5

In the same study done in Benin, the researchers

found no significant differences between the mean cord

T

2

7,29

.

3 4

blood T , T , and TSH and the mean serum values of

to T

3

than T

4

these hormones at 72hours (p=0.36, 0.08, 0.33 respec-

tively), meaning that it makes no difference whether

screening for congenital hypothyroidism is done with

cord blood or venous blood at 72hours, consequently the

same reference values may be utilized. This is however,

contrary to this present study which demonstrated differ-

ences between the cord blood and 72hours mean con-

The finding of low T

ports that the fetus is T

3

at birth confirms the earlier re-

deficient most likely due to the

to T in the extra thy-

3

reduced capacit₉y to de-iodinate T

4

3

2

roidal tissues. The rapid increase in serum T

3

after

to T

is due

secretion from the thyroid

gland stimulated by the TSH surge rather than₂i₉ncreased

conversion of T to T in the peripheral tissues.

The subsequent decline in T

delivery at a time when the capacity to convert T

4

3

is reduced suggests that the increment in serum T

predominantly to increased T

3

centrations of T

The mean T however was not significantly different

from the cord blood levels (p=0.29). The reasons for the

differences in findings of the two studies ( present

3

and TSH (p=0.05, 0.001 respectively).

3

4

3

to levels above c₇_,o₂₉rd blood

2

study and Benin study) is not quite clear, but may be

related to the smaller number of AGA neonates (38)

recruited in this study, compared to the larger number in

the Benin study (114), the varying modes of delivery in

this study (CS, SVD, vacuum). All the subjects enrolled

in the Benin study were delivered by SVD. Conflicting

reports have earlier been documented by various

at 72hours, is consistent with earlier reports , and is

due to the waning of the physiologic TSH surge usually

1

8

at 48-72 hours . The declining levels of T

with falling TSH seems to agree with this explanation.

The decline in serum T at 72 h₂o₇_,u₇ rs is consistent with

earlier report by Jacobsen et al The fact that mean

3

coinciding

4

TSH at 72 hours fell to about half the cord level is a

reflection of the fact that necessary homeostatic tem-

perature adjustments are complete and the stimulus for

physiologic surge of TSH, removed. Therefore, newborn

researchers on the effect of mode of delivery on thyroid

3

1-33

.

function

2

13

Conclusion

particularly where cord TSH is missed (e.g. home deliv-

eries), and the results should be interpreted using post

mean T

hours in term healthy neonates, while T

3

levels peaked at 24 hours and decreased at 72

levels increased

natal age appropriate reference ranges. Serum T3, T

4

and repeat TSH should then be assayed for confirmation

in all neonates with a positive TSH screening. There

should be vigorous pursuit of further multicenter col-

laborative evaluations of neonatal thyroid function in

Nigeria.

slightly but progressively from birth to 24hours and de-

clined at 72 hours. However, the mean TSH levels

peaked at 24 hours before declining at 72 hours to lower

than cord blood levels. It is therefore recommended that

serum TSH assayed at or greater than 72hours may be

utilized for screening for congenital hypothyroidism,

Conflict of interest: None

Funding: None

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