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British Journal of Healthcare and Medical Research - Vol. 10, No. 2
Publication Date: April 25, 2023
DOI:10.14738/jbemi.102.14449.
Giusti, M. (2023). Survey on a Cohort of Subjects Aged From 6 Months to 18 Years and Born to Mothers Managed for Thyroid Hypo- Function in Pregnancy. Experience in a Single Non-Academic Centre in Liguria, Italy. British Journal of Healthcare and Medical
Research, Vol - 10(2). 402-420.
Services for Science and Education – United Kingdom
Survey on a Cohort of Subjects Aged From 6 Months to 18 Years
and Born to Mothers Managed for Thyroid Hypo-Function in
Pregnancy. Experience in a Single Non-Academic Centre in
Liguria, Italy
Massimo Giusti
Endocrine Unit, Clinical Diagnostic Centre Priamar, via dei Partigiani
13R, I-17100, Savona, Italy, and Department of Internal Medicine,
University of Genoa, Genoa, Italy
Orcid: 0000-0002-1269-8376
ABSTRACT
Background: The adequate management of thyroid dysfunction in pregnancy
reduces pre-partum adverse events and improves the life of the new-born. Aim:
Women managed for thyroid hypo-function during pregnancy were retrospectively
identified and a survey was performed on their offspring aged from 6 months to 18
years. Methods: We selected 131 pregnancies for survey. From January to August
2022, the mothers were sent a questionnaire containing questions on the neonatal
and post-natal period and questions on their children's current auxological,
scholastic and pathological status and lifestyle. Eighty-two questionnaires were
returned. The mothers’ replies were compared with their f-T4 and TSH levels
recorded during pregnancy. Reference f-T4 and TSH values were extrapolated from
76 pregnancies managed according to current guidelines. Results: f-T4 values
below the 2.5th percentile were found in less than 3% of cases, while f-T4 values
above the 97.5th percentile were found in less than 4%. TSH proved more variable.
Replies regarding the time of the new-born’s first postural changes were
significantly inversely correlated with f-T4 concentrations in each trimester of
pregnancy and positively correlated with the TSH levels observed in the 1st
trimester. Conclusions: This single-centre, cross-sectional, study offers further
indications for the management of thyroid hypofunction in pregnancy and suggests
that the control of maternal f-T4 and TSH levels during pregnancy has improved in
our district. Data from survey indicate that f-T4 influences early motor activity in
new-borns more than TSH does. However, the small sample size, the wide age range
of the children and the long time-lag between delivery and survey administration
could impair our results.
Keywords: Thyroid function, Pregnancy outcome, Offspring outcome, post-natal survey.
BACKGROUND
Although the utility of universal screening of thyroid function in pre-pregnancy is still debated,
the increase in age on pregnancy and the growing diffusion of reproductive technologies have
increased the need for thyroid examinations in women who wish to become pregnant [1, 2].
Several guidelines have been published to guide decisions to prevent thyroid dysfunction
during pregnancy [3-5].
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403
Giusti, M. (2023). Survey on a Cohort of Subjects Aged From 6 Months to 18 Years and Born to Mothers Managed for Thyroid Hypo-Function in
Pregnancy. Experience in a Single Non-Academic Centre in Liguria, Italy. British Journal of Healthcare and Medical Research, Vol - 10(2). 402-420.
URL: http://dx.doi.org/10.14738/jbemi.102.14449.
Hypothyroidism, more than hyperthyroidism, is frequently observed in women of reproductive
age, and the treatment of overt disease before and during pregnancy is mandatory. However,
how subclinical thyroid diseases should be treated is still debated. Subclinical hypothyroidism
(SCH) and isolated hypothyroxinaemia (decreased f-T4 levels with normal TSH levels) are the
most frequent thyroid dysfunctions encountered in pregnancy [6]. On analysing 47,045
pregnant women, 3.1% of whom had SCH, 2.2% isolated hypothyroxinaemia and 7.5% positive
thyroid peroxidase antibody (TPOAb) titres, Korevaar et al. [7] observed a higher risk of pre- term birth. Ge et al. [8] found an increased risk of neuro-developmental disorders in the
offspring of SCH mothers with inadequate control of hypothyroidism (TSH levels >4 mIU/l) and
underlined the need for routine measurement and timely treatment of thyroid hypofunction in
pregnancy. Similarly, Maraka et al. [9] confirmed that SCH in pregnancy was associated with
multiple maternal and neonatal adverse outcomes, but failed to ascertain the role of levo- thyroxine (L-T4) therapy in preventing these outcomes. On the other hand, some researchers
have reported that L-T4 treatment in SCH pregnant women could improve maternal and
neonatal adverse outcomes [10, 11], but many controversial data have emerged on the possible
detrimental effects (increased risk of pre-term delivery, small for gestational age neonates, pre- term delivery, gestational diabetes and pre-eclampsia) of potential L-T4 over-treatment [8, 12,
13].
The TSH values above which L-T4 treatment should be started are indicated in the 2017
American Thyroid Association (ATA) guidelines and population- and trimester (Tr)- specific
cut-offs are recommended for monitoring therapy [3]. An overview of published gestational
TSH and f-T4 reference intervals has recently been published [14]. References intervals for TSH
and f-T4 in pregnancy vary widely, owing to differences in assay methods, inclusion/exclusion
of antibody-positive women or women with thyroid diseases in pregnancy, iodine status, body
mass index (BMI) and other additional criteria, and the percentile range used [14-16]. In
addition, extrapolating published reference intervals to local reality is quite difficult, and over- or under-treatment in subclinical thyroid dysfunction is somewhat a risk. In a retrospective
(1999-2019) analysis of the real-world management of pregnant hypothyroid women in a
secondary endocrine centre in our region (Savona district, Liguria, Italy), we observed that
adherence to guidelines improved over time, and L-T4 over-treatment decreased [17].
However, several concerns remained, such as infrequent pre-gestational endocrine
examinations, referral to the endocrinologist for out-of-range TSH levels late in pregnancy and
scant perception of the need for iodine supplementation [17]. Moreover, no significant
differences in adverse obstetric or perinatal outcomes were noted in medical records collected
over a long period of time [17]. The aim of the present study was to extend previous
observations in women attending the same non-academic secondary centre from the pre- gestational period to delivery for the management of thyroid dysfunction, mainly SCH, by
providing data on post-natal outcomes, as self-reported by mothers. A secondary aim was to
quantify trimester-specific f-T4 and TSH intervals and compare post-natal outcomes with
individual hormonal values in pregnancy.
MATERIAL AND METHODS
Subjects
This cross-sectional study was conducted at the Endocrine Unit of Priamar Clinical Diagnostic
Centre, a private secondary-level out-patient centre located in the Savona district (Liguria,
Italy). From medical files collected from 2000-2022, we identified women of childbearing age
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British Journal of Healthcare and Medical Research (BJHMR) Vol 10, Issue 2, April- 2023
Services for Science and Education – United Kingdom
who were treated for thyroid dysfunction; 151 had been managed for 193 pregnancies. They
were referred to the centre before or during pregnancy by general practitioners or
gynaecologists for the evaluation and management of thyroid dysfunction. Initial exclusion
criteria were: mother's age less than 18 years; twin or higher-order gestations; except for L-T4,
administration of other medications known to affect thyroid function during pregnancy. Figure
1 details the pregnancies excluded for various reasons and when offspring were aged less than
6 months or over 18 years. After these exclusions, 131 questionnaires were sent to the known
email addresses, from January to August 2022. This period was chosen so that the mothers'
judgements of scholastic performance could be referred certainly to the last school year, after
the schools had closed for holidays. Finally, 82 questionnaires were completed and returned
(Figure 1).
Figure 1 Flowchart of the study.
In these women, the average age at the time of pregnancy was 35.3 ± 4.4 years (±SD; range 25-
46 years). Thyroid diagnoses were: Hashimoto’s thyroiditis (HT; n=54), uni-nodular or multi- nodular goitre (n=14), thyroid ultrasonography (US) indicative of HT but with negative thyroid
antibodies (n=10), and post-surgical hypothyroidism (n=4). In 70% of pregnancies, a pre- gestational examination was available; in 77% of pregnancies, L-T4 treatment was ongoing
after the finding of a positive β-human chorionic gonadotropin value. Thyroid function was
managed in accordance with the available literature data [3, 18, 19] and as previously reported
[17]. In general, during the pre-pregnancy examination, women were informed of the need to
start L-T4 or to increase their L-T4 dosage when pregnancy began. After the first adjustment,
L-T4 was increased arbitrarily by 25 μg/week per 2 kg gain in body weight during pregnancy
[17]. An iodine intake of >150 μg/day was recommended during the pre-gestational visit
and/or at the first examination during pregnancy. Prenatal endocrine examination was
performed in the 1st trimester (median 8 weeks; IQR 6-10 weeks, range 4-12 weeks) in the