|
Indian Pediatr 2015;52:
864-866 |
|
Maternal Overt Hypothyroidism and
Neurobehavioral Outcome of Neonates: A Cohort Study from an
Iodine-deficient Area of Northern India
|
*Mohammad Ashraf Ganaie, Bashir A Charoo, Riyaz Ahmad
Sofi, Asif Ahmed and Javeed Iqbal Bhat
From Department of *Endocrinology, AIIMS, New Delhi;
and Department of Pediatrics, Sher-i-Kashmir Institute of Medical
Sciences, Srinagar, J&K; India.
Correspondence to: Dr Javeed Iqbal Bhat, Department
of Pediatrics, SKIMS Soura, Jammu and Kashmir 190 011, India. Email:
[email protected]
Received: October 15, 2014;
Initial review: December 4, 2014;
Accepted; August 20, 2015.
|
Objective: To study the relation between maternal overt
hypothyroidism and neurodevelopmental outcome of neonates in
iodine-deficient region of Northern India (Kashmir Valley).
Design: Prospective cohort study.
Setting: Endocrinology department of a
tertiary-care hospital.
Participants: 82 hypothyroid pregnant women were
enrolled and followed up till delivery. The neonates born to this group
represented the case neonates. 51 euthyroid healthy pregnant women were
selected as control group. The neonates born to these mothers served as
controls.
Main outcome measures: Early neonatal behavioral
assessment at 3-4 weeks of age.
Results: The mean TSH and free T4 in neonates of
mothers with well controlled hypothyroidism was significantly different
from those born to mothers with poorly controlled hypothyroidism and
controls in 1st trimester, but the difference was statistically
insignificant for 2nd and 3rd trimester values.
Conclusion: Overt maternal hypothyroidism in
iodine-deficient area constitutes a risk factor for an abnormal
neurobehavioral development of affected child.
Keywords: Infant, Iodine deficiency, Neurodevelopment,
Pregnancy, Prognosis.
|
H ypothyroidism is a relatively common condition
among pregnant women [1,2]. During pregnancy, thyroid gland is subjected
to stress and undergoes adaptation to maintain sufficient output of
thyroid hormones for both the mother and the fetus [3]. In
iodine-deficient areas like sub- Himalayan belt, predominant cause of
hypothyroidism among pregnant women is iodine deficiency [5]. Studies
have established the link between maternal hypothyroidism and adverse
neurobehavioral outcome of the affected child [6]. Most of such studies
were conducted in iodine sufficient areas where autoimmune thyroiditis
is a predominant cause of hypothyroidism. We aimed to study the relation
between maternal overt hypothyroidism and neurodevelopmental outcome of
neonates in an iodine deficient region [7] of Northern India (Kashmir
valley).
Methods
This prospective study was conducted over a period of
2 years at Sher-i-kashmir Institute of Medical Sciences Srinagar, a
tertiary-care hospital in Northern India. The study cohort was selected
from the Endocrinology department of the Institute. Eighty-two
hypothyroid pregnant women receiving thyroxine/no treatment were
enrolled and followed up till delivery. The neonates born to this group
represented the case neonates. Fifty-one euthyroid healthy pregnant
women, free from any systemic disease, were selected as controls from
the same institute. The neonates born to these mothers served as control
neonates.
Ethical clearance was obtained from institutional
ethical committee (IEC) and written informed consent was taken from all
participants. All pregnant women were closely followed till delivery and
their neonates were followed up till 1 month of age.
The study participants were categorized into
following subgroups: Group A (n=43) – known hypothyroid
women on treatment but uncontrolled at presentation and women first time
diagnosed with hypothyroidism during first trimester of pregnancy;
Group B (n=39) – known hypothyroid women on treatment having
good control; and Controls (n=51) – euthyroid women
without any treatment. Neonates: 132 neonates born to case (81)
and control (51) group mothers were included in this study. There was
one still birth in the case group.
In each trimester, estimation of serum TSH and free
thyroxine (FT4) levels were done by chemiluminescence method.
Simultaneously, 3 mL of urine was also collected in each trimester and
immediately stored at –70 0C
for urinary iodine estimation. Urinary iodine estimation was done by
Sandell-Kolthoff reaction principle and all the stored samples were
processed together at the end of study period. All the enrolled neonates
underwent thyroid screening anytime from 2nd
day to 6th day of life by
above mentioned method. Levels less than 10 mU/L were considered to be
normal, 10-20 mU/L were considered borderline and >20 mU/L were labelled
as abnormal. Borderline group was recalled for estimation of thyroid
status after 2-4 weeks.
Early neonatal behavioral assessment was done at 3-4
weeks of age using Brazelton’s Neonatal Behavioral Assessment Scale
(NBAS). The scale contains 7 clusters of 31 items, both neurological and
supplementary, that measures the quality of responsiveness and the
amount of input that the infant needs from the examiner to show his or
her best performance. All of the items were scored in the correct state
as defined in the NBAS guidelines. ANOVA (analysis of variance) was used
for parametric data and Kruskal Wallis test was used for non-parametric
data after checking for Gaussian distribution with the help of
Shaprio-Wilk and Kolomogrov-Smirnov tests. Graph-pad prism statistical
software was used for analyses.
Results
This hospital-based study comprised of 82 mothers
with hypothyroidism and 51 control mothers. The mean (SD) age of cases
and controls was 29.4 (3.5) and 29.9 (3.4) years, respectively.
Table I compares anthropometric parameters in case and control
neonates. Table II presents thyroid function tests in the
mothers in 1st, 2nd and 3rd trimester. The mean TSH in group A was
higher in 1 st trimester than
Group B and controls but the difference was statistically insignificant
in 2nd and 3rd
trimester. First trimester FT4 levels were lower in group A compared to
group B pregnant women and controls. In all three groups, mean urinary
iodine excretion in all trimesters was less than 150 µg/dL. Total T4 was
significantly higher in group A and Group B Neonates than control
neonates. The mean (SD) NABS score in group A [19.6 (2.15)] was
significantly lower than group B [21.3 (3.72)] (P.0.037) and
group C [24.0 (3.20)] (P <0.001). Moreover, the NABS scrore in
group B was also significantly lower than controls (P<0.001).
TABLE I Anthropometric Parameters in the Three Groups
|
Group A (n=43) |
Group B (n=39) |
Control (n=51) |
P value |
Weight (kg), mean (SD) |
2.42 (0.31) |
2.67 (0.38) |
2.79 (0.41) |
<0.001 |
Length (cm), mean (SD) |
47.8 (1.66) |
48.4 (1.46) |
48.2 (1.61) |
0.25 |
Head circumference (cm), mean (SD) |
33.7 (1.51) |
34.2 (1.26) |
34.3 (1.11) |
0.07 |
Gestational age (wks), mean (SD) |
36.0 (1.75) |
36.7 (0.98) |
36.7 (0.70) |
0.02 |
Group A= Born to mothers with uncontrolled hypothyroidism at
presentation;. Group B = Born to mothers with good control at
presentation; Control=Born to euthyroid mothers. |
TABLE II Comparison of Thyroid Function Parameters [Meadian (IQR)] in the Three Groups
Variable |
Group A, n=43 |
Group B, n=39 |
Control, n=51 |
P value |
1st trimester TSH (µIU/mL) |
7.13 (3.93) |
3.60 (2.78) |
4.50(1.12) |
<0.001 |
1st trimester FT4 (ng/dL) |
1.09 (0.31) |
1.26 (0.43) |
1.47 (0.32) |
<0.001 |
1st trimester urinary iodide (mcg/L) |
139.2 (23.05) |
144.7 (19.5) |
144.2 (17.31) |
0.078 |
2nd trimester TSH (µIU/mL) |
5.04 (4.22) |
3.98 (2.66) |
4.87 (0.65) |
0.070 |
2nd trimester FT4 (ng/dL) |
1.08 (0.30) |
1.07 (0.32) |
1.11 (0.20) |
0.276 |
2nd Trimester Urinary Iodide (mcg/L) |
127.1 (20.8) |
131.7 (21.0) |
133.09 (16.70) |
0.054 |
3rd Trimester TSH (µIU/mL) |
5.55 (3.91) |
4.62 (3.1) |
5.25 (0.46) |
0.127 |
3rd Trimester FT4 ( ng/dL ) |
1.06 (0.23) |
1.06 (0.2) |
1.11 (0.23) |
0.092 |
3rd Trimester Urinary Iodide (mcg/L) |
117.0 (24.97) |
120.0 (21.2) |
121.40 (16.79) |
0.027 |
Group A= uncontrolled hypothyroidism. Group B = controlled
hypothyroid; Control = Euthyroid pregnant women. |
Discussion
Our study demonstrates that iodine deficiency is
still prevalent in our population and iodine intake in our pregnant
women is inadequate as median urinary iodine level was less than
recommended median value of 150 µg/L [8] in all the 3 groups of
patients. We also demonstrated that neurobehavior development of
neonates born to hypothyroid mothers is lower in comparison to euthyroid
mothers.
These results are in agreement with an earlier study
[6] in which maternal hypothyroxinemia (low FT4, normal TSH) in the
first trimester was associated with decreased NBAS (orientation) scores.
However, this study was conducted in an iodine-sufficient area and
included women with hypothyroxinemia of pregnancy with no overt
hypothyroidism. Mothers in our study were overt hypothyroid with
markedly elevated TSH and decreased FT4 in first trimester, and most of
them were on thyroxine replacement.
The limitation of our study was that neurobehavioral
assessment in our cohort was done between 3-4 weeks of postnatal age
that may not be representative of future neurodevelopment of a child.
Studies where assessment was done at a later age also support this
observation [9,10]. Long term follow-up studies evaluating the causal
link between maternal hypothyroidism and adverse neurodevelopmental
outcome in the affected offsprings are required.
To conclude, our study suggests an important link
between early maternal hypothyroidism and neurobehavioral outcome of
affected offsprings. We recommend early identification of hypothyroidism
in pregnant women, especially in endemic areas. and their optimal
treatment to improve developmental outcome of their children.
Contributors: MAG, BAC: conceived and designed
the study, and reviewed the manuscript for important intellectual
content; RAS: carried out the analyses and prepared the Methods
and Results sections of the text. AA, JIB: collected data and
drafted the paper. The final manuscript was approved by all the authors.
Funding: None; Competing interests: None
stated.
What is Already Known?
• Hypothyroxinemia of pregnancy is a risk
factor for adverse neurodevelopmental outcome in offspring.
What This Study Adds?
• Maternal overt hypothyroidism in this
iodine-deficient area was associated with adverse
neurodevelopmental outcomes in the offspring.
|
References
1. Klein RZ, Haddow JE, Faix JD, brown RS, Hermos RJ,
Pulkkinen A, et al. Prevalence of thyroid deficiency in pregnant
women. Clin Endocrinol.1991;35:41-6.
2. Allan WC, Haddow JE, Palomaki GE, Williams JR,
Mitchell MI, Hermos RJ, et al. Maternal thyroid deficiency and
pregnancy complications; Implications for population screening. J Med
Screen. 2007;7:127-30.
3. Poppe K, Glinoer D, Tournaye H, Schittecatte J,
Haentigens P, Velkeniers B. impact of ovarian hyper stimulation on
thyroid function in women with or without thyroid autoimmunity. J Clin
Endocrinol Metab. 2004;89:3808-12.
4. Vermiglio F, Lo Presti VP, Scaffidi Argentina G, Finocchiaro
MD, Gullo D, Squatrito S, et al. Maternal hypothyroxinaemia
during the first half of gestation in an iodine deficient area with
endemic cretinism and related disorders. Clin Endocrinol. 1995;42:409-15.
5. Mehdi T, Hoque MM, Nasreen ZA, Shirin F, Khan MMH.
Maternal iodine status and thyroid function during pregnancy. J
Medicine. 2009;10:56-9.
6. Kooistra L, Crawford S, van Baar AL, Brouwers
EP, Pop VJ. Neonatal effects of maternal hypothyroxinemia during early
pregnancy. Pediatrics. 2006;117:161-7.
7. Bashir H, Farooq R, Bhat MH, Majid S. Increased
prevalence of subclinical hypothyroidism in females in mountainous
valley of Kashmir. Indian J Endocrinol Metab. 2013;17:276–80.
8. Geneva: World Health Organization. Urinary Iodine
Concentrations for Determining Iodine Status Deficiency in Populations.
2013 Available from:
http://www.who.int/nutrition/vmnis/indicators/urinaryiodine.MH/NHD/EPG/13.1.
Accessed April 13, 2015.
9. Finken MJ, van Eijsden M, Loomans EM, Vrijkotte
TG, Rotteveel J. Maternal hypothyroxinemia in early pregnancy predicts
reduced performance in reaction time tests in 5- to 6-year-old
offspring. J Clin Endocrinol Metab. 2013;98:1417-26.
10. Henrichs J, Bongers-Schokking JJ, Schenk JJ, Ghassabian
A, Schmidt HG, Visser TJ, et al. Maternal thyroid
function during early pregnancy and cognitive functioning in
early childhood: The generation R study. J Clin Endocrinol Metab. 2010;95:4227-34.
|
|
|
|