Fetomaternal Outcome in Maternal Hypothyroidism Complicating Pregnancies at Paropakar Maternity and Women’s Hospital ()
1. Introduction
Thyroid disorders constitute one of the most common endocrine disorders in pregnancy and thyroid physiology plays a major role in pregnancy alteration in thyroid functions occurs due to increased thyrotropic effect of human chorionic gonadotropin (HCG), increased thyroid hormone binding globulin (TBG) concentration, and increased iodine clearance in the kidneys [1]. Fetus depends on maternal thyroid hormone for organogenesis, general growth, and development of a central nervous system since fetus synthesizes thyroid hormone only by the end of the first trimester [2] [3].
The prevalence of thyroid dysfunction is high in pregnant women, with subclinical dysfunction in 10% of pregnancies and overt in 2% - 3% of pregnancies [4]. Subclinical hypothyroidism occurs in 3% - 5% of pregnancies and overt hypothyroidism in 0.3% - 0.5% [5].
TSH level of 2.5 mIU/L in the first trimester and TSH level of 0.2 - 3 mIU/L in the second trimester and free thyroxine (FT4) as 12 - 30 pmol/l has been accepted according to the guideline of the American thyroid association published in 2011 for an accurate diagnosis and management of thyroid disease in pregnancy [6].
Various studies have shown that hypothyroidism in pregnancy leads to adverse maternal outcomes including anemia, gestational hypertension, gestational diabetes mellitus, placenta previa, placental abruption, premature rupture of membrane, premature delivery, LSCS delivery, and postpartum hemorrhage. Similarly, adverse perinatal outcomes including IUGR, LBW, fetal distress, prematurity, stillbirth, malformation, congenital hypothyroidism, neonatal thyrotoxicosis, and neurocognitive defects are also seen [7] [8].
With this background, this study aimed to find the fetomaternal outcome in pregnancy complicated by maternal hypothyroidism.
2. Methods
This was a retrospective observational study conducted at Paropakar Maternity and Women’s Hospital (PMWH), Thapathali, Kathmandu from July 2020 to April 2021. Institutional approval was taken for the study (60/1692).
All singleton pregnant women with hypothyroidism delivered at the institution during the study duration were included. Molar pregnancy, hyperthyroid pregnant women, multiple gestations, women with diagnosed chronic hypertension, diabetes mellitus, and previous bad obstetric history with a known underlying cause were excluded from the study. The Sample size was calculated by the prevalence method for hypothyroidism in pregnancy.
Pregnant women in their antenatal visit were screened with TSH, free T3, and free T4 levels with additional TPO antibody when required. As per the ATA, guideline women were categorized as having overt hypothyroidism TSH > 3 mIU/L with a low FT4 or a TSH ≥ 10 mIU/L irrespective of FT4 levels, subclinical hypothyroidism (TSH of 3-10 MIU/L and a normal FT4 levels), normal (TSH of 0.2 to 3 mIU/L and FT4 of 11.84 ± 3.86).
Data were recorded in a predesigned pro forma. Obstetric outcomes and perinatal outcomes were noted for hypothyroid mothers including the mode of delivery, and postpartum hemorrhage. Neonatal assessment with APGAR score, birth weight, and presence of congenital anomalies was also noted. Chi-square test and Fisher exact test were applied for data analysis and statistically analyzed using SPSS. P-value of < 0.05 was regarded as statistically significant. The ethical clearance was taken from the Institutional Review Committee (IRC) of Paropakar Maternity and Women’s Hospital before starting the study.
3. Results
A total of 470 cases of hypothyroidism were admitted for delivery, among which only 330 were enrolled for the study, and the remaining 140 cases were excluded. Total population delivered were 22200 in 1 year. So the prevalence is calculated as follows:
So the prevalence of hypothyroidism in pregnancy was 2.11% of total deliveries with 1.7% of subclinical and 0.31% of overt hypothyroidism.
In present study most of the cases belonged to age group >30 years 57.9% (n = 191), followed by 20 - 29 years 36.4 % (n = 120) and less than 20 years 5.8% (n = 19). Similarly, 70.3% (n = 232) of the cases were from rural areas and 29.7% (n = 98) of the cases were from urban areas. Primigravida constituted 53.3% (n = 176) of the cases, followed by multigravida-2 (27.9%), multigravida-3 (13%) and multigravida −4 (5.8%). A regular menstrual cycle was found in 59.1% (n = 195) of the cases whereas 40.9% (135) had an irregular cycle.
In the present study, 85.8% (n = 283) had subclinical hypothyroidism and 14.2% (n = 47) had overt hypothyroidism. The mean TSH levels in these subgroups were 4.654 and 5.99 respectively (Table 1).
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Table 1. Thyroid profile inference and mean TSH Levels.
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Table 2. Maternal adverse outcomes seen with hypothyroidism in study participants.
Preeclampsia, Gestational Diabetes Mellitus, Abruptio placenta, and Postpartum Hemorrhage were the adverse maternal outcomes found in hypothyroid mothers with a higher percentage of these in overt hypothyroidism (Table 2).
Instrumental delivery was performed in 6.3% of participants with overt and 2.1% with subclinical hypothyroidism. Cesarean delivery was performed for 53.1% of overt and 46.2% of subclinical hypothyroid participants, indicating a higher cesarean rate in these women.
Preterm delivery 29.7% were observed in overt hypothyroidism while 11.2% was observed in subclinical hypothyroidism which was statistically significant (Table 3).
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Table 3. Gestational age at delivery.
Hypothyroid mothers were also found to have adverse perinatal outcomes including congenital anomaly, IUFD, IUGR, NICU admissions, neonatal respiratory distress syndrome (RDS), and a low APGAR at 6 minutes of life (Table 4).
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Table 4. Perinatal outcome in hypothyroid mothers.
Neonatal weight of <2.5 kg was found in 42.5% and 19.7% of women with overt and subclinical hypothyroidism respectively reaching a statistical significance with a P-value of 0.001. Among participants with overt hypothyroidism, a birthweight of 2.6 - 3.5 kg was seen in 53.1% and 3.6 - 4.5 kg in 4.2%. Similarly, with subclinical hypothyroidism, the birthweight was 2.6 - 3.5 kg in 63.6% and 3.6 - 4.5 kg in 16.6%.
4. Discussion
Hypothyroidism in pregnancy can be masked under certain physiological changes from the pregnancy itself like weight gain, muscle cramps, constipation, or fatigue emphasizing the importance of screening with the thyroid function test. Our study consisted of 330 antenatal patients undergoing screening for thyroid dysfunction. The incidence of hypothyroidism among the study population was 1.7% for subclinical and 0.31% for overt hypothyroidism. Similar to our study, Shrestha A et al. had an incidence of 1.9% for hypothyroidism in pregnancy [9].
The majority of the patients in the present study were above 30 yrs age (51.3%) with a mean age of 28.9 years, which was also observed in a study done by kalpesh et al. that showed increased maternal age associated with thyroid dysfunction [10]. The majority belonged to rural areas (70.3%) whereas urban areas accounted for 29.7%. Overt Hypothyroidism had a higher incidence compared to subclinical hypothyroidism for preeclampsia (11.8%), gestational diabetes mellitus (11.5%), and postpartum hemorrhage (4.5%). Endo T et al. showed that hypothyroidism can lead to hypertension [11]. Similarly, Wolfberg et al concluded that women who were treated for hypothyroidism were more likely to have chronic hypertension and increased risk for preeclampsia [12]. However, our study had a much higher incidence compared to their study (4.3%). Although another study by Cleary Goldman and colleagues documented a greater risk of GDM with overt hypothyroid and no such association with SCH [13].
In the study by Casey et al, the risk for placental abruption in hypothyroidism was increased by 3 times, while preterm birth was increased two-fold. [14] Our study had 7 cases (2%) of placental abruption and preterm delivery was seen in 13.9%.
Although the incidence of IUGR was 2.9% as per the study by Shrestha A et al., our study had a higher overall incidence of 14.5% with 31.9% among the population who had overt hypothyroidism [9]. Similar to our study Ohashi et al. reported IUGR in 25% of pregnancies involving maternal thyroid disorder [15]. This could be due to thyroid hormone which is responsible for the metabolism along with fetal weight. Similarly, hypothyroid mothers in our study showed an adverse effect on perinatal outcomes including IUFD (3.3%), NICU admissions (12.1%), and APGAR score of less than six at five minutes (22.1%). Shrestha A et al. also studied a low APGAR of 11.3% in their study [9]. Congenital anomaly was noted in 2.4% hypothyroid study population in our study. Su and colleagues also reported malformation in a fetus (1 case of circulatory system and 2 cases of musculoskeletal system) mainly in women with overt hypothyroid [16]. However, the study by Casey et al suggested that maternal thyroid disorder was not associated with an increased rate of fetal malformation [14].
More studies with larger sample sizes and longer duration of study should also be done for more targeted research.
5. Conclusion
Undiagnosed and untreated hypothyroidism in pregnancy can lead to adverse maternal and fetal outcomes with increased risk of preeclampsia, gestational diabetes mellitus, preterm birth, postpartum hemorrhage, IUFD, IUGR, poor APGAR score, and NICU admissions. In endemic iodine deficient countries like Nepal, screening with TSH during pregnancy can diagnose and ultimately reduce the adverse outcomes associated with hypothyroidism with early treatment.