European Journal of Cardiovascular Medicine

Pregnancy induces significant physiological stress on mother and fetus, with notable changes in thyroid function. Thyroid hormone levels fluctuate, increasing around the 12th week and decreasing in the latter half of pregnancy. These changes make diagnosing hypothyroidism challenging. Thyroid hormone deficiency during pregnancy can be categorized into clinical hypothyroidism, subclinical hypothyroidism, and isolated hypothyroxinaemia, each with distinct hormone level profiles. Proper management is crucial to prevent serious consequences.^{1- 3}

Thyroid hormone is essential for fetal development, particularly in promoting protein synthesis, tissue formation, and brain cell growth. During early pregnancy, the mother's thyroid hormone plays a vital role in supporting fetal brain development, as the fetus's thyroid gland is immature and relies on maternal thyroid hormone transferred through the placenta. This maternal support is crucial until the fetus's thyroid gland matures and can produce its own thyroid hormone, highlighting the importance of adequate maternal thyroid function during pregnancy.⁴ Maternal thyroid hormone insufficiency, particularly in later pregnancy stages, can impact fetal development, potentially leading to neurodevelopmental abnormalities and affecting physical and intellectual growth. Children born to mothers with thyroid hormone inadequacy may experience delays or deficits in development and response to environmental stimuli. Additionally, thyroid hormones play a crucial role in forming long bones and teeth, underscoring their importance for overall fetal development.⁵

Maternal hypothyroidism has been linked to various adverse outcomes, including neonatal jaundice, hypocalcemia, respiratory distress, and increased risk of congenital anomalies. Offspring may also experience cognitive and motor impairments. Diagnosing hypothyroidism during pregnancy can be challenging due to overlapping symptoms with normal pregnancy, such as fatigue, constipation, and weight gain, making laboratory testing crucial for accurate diagnosis.^6-8

Untreated hypothyroidism is associated with several complications, most notably, perinatal mortality, preterm delivery, low birth weight, Persistence of physiological jaundice, Difficulty in feeding, Delayed milestones in physical development. Treatment of pregnant mothers with l-thyroxine reduces these complications substantially. Enough evidence has accumulated over the years about the role of thyroxine in normal development of the fetal brain. This study aims to evaluate the neonatal outcomes in babies born to hypothyroid mothers at a tertiary care center 

The study was conducted in Neonatal Intensive Care Unit (Dept. of Pediatrics) at Maharishi Markandeshwar Institute of Medical Sciences and Research, Mullana, Ambala. This was a hospital based clinical observational study conducted over one and a half year.

All pregnant mothers were screened for hypothyroidism before 18 weeks of gestation and mothers with evidence of hypothyroidism were included in the study. Infants born to mothers with Hypothyroidism were included in the study. Babies with conditions like birth asphyxia, congenital anomalies, sepsis, infants of diabetic mother, mothers taking anticonvulsant drugs and neonates having metabolic disorders were  excluded from the study.The study included 50 neonates with hypothyroid mother.Another set of 50 neonates born to pregnant subjects with absence of maternal hypothyroidism or any other thyroid related disorder were included as controls. Trimester-specific reference interval for thyroid function tests was taken and for TSH it was as follows: 0.05-4.24, 0.13-3.95, and 0.20-3.00 uIU/mL in each trimester respectively (ATT guidelines 2017). Details regarding maternal treatment was obtained from maternal records. Anthropometric data of the neonates was obtained. Neonatal outcome was assessed.

All the results were recorded and analyzed using SPSS software. Chi-square test and student t test were used for evaluation of level of significance. P-value of less than 0.05 was taken as significant

In this study, among 50 mothers from maternal hypothyroid 35 (70%) belong to urban residence and 15 (30%) belong to rural .While among the control group 36(72%) mothers are from urban group and 14 (28%) mothers from rural group. . There is no statistically significant difference between the residence in the two groups. (p=0.82)Among maternal hypothyroid group 33 mother had undergone caesarean section while remaining 17 had vaginal delivery .In control group 43 mothers had vaginal delivery and remaining 7 underwent caesarean section There is statistically significant Caesarean deliveries in hypothyroid mothers as compared to control group. (p=0.001).Among 50 maternal hypothyroid mother 41 neonates were born at term gestation , 6 were born at late preterm and 3 neonates were moderate preterm . On the other hand in the control group among 50 neonates, 48 were born at term gestation , 2 were born at late preterm. Maternal hypothyroid group, 6 percent were born moderate preterm, 12 percent were late preterm neonates and 82 percent were term neonates. Control group, 4 percent are born at late preterm and 96 percent are born at term. There was statistically significant preterm deliveries in maternal hypothyroid group as compared to control group (p-value=0.001)  Maternal hypothyroid group has 28 boys and 22 girls while control group has 24 boys and 26 girls.There is no statistical difference was seen in gender distribution of neonates(p=0.12)

Table 1: Distribution of neonates as per different parameters among the two groups

Among 50 neonates of maternal hypothyroid group, 35 neonates were normal birth weight and rest 15 neonates were Low birthweight . In control group one neonate is found to be low birth weight while 49 neonates were normal birth weight. There is Statistically Significant difference in birth weight in hypothyroid mother compared to neonates born to non hypothyroid mother. (p=0.00). Among 50 neonates of maternal hypothyroid group, 40 neonates were appropriate for gestational age , 10 neonates were small gestational age. In control group all neonates were appropriate were gestational age. There is statistically significant difference in Weight for gestational age in maternal hypothyroid group compared to control group.There are more SGA babies in maternal hypothyroid group . (p=0.000)

Table 2: Athropometric parameters of neonates among the two groups

Mean weight among patients of the maternal hypothyroidism group is 2.68 and mean weight of control group is 2.90 . There is statistically significant difference seen in weight of neonate born to hypothyroid mother and neonates born to non hypothyroid mother (p=0.01) Mean length and head circumference among patients of the maternal hypothyroid group was 48.32 cm and 35.19 cam respectively while among control group, mean length and head circumference among patients of the maternal hypothyroid group was 46.75 cm and 34.39 cm respectively. There is no statistically significant difference in length p=0.820 and head circumference p=0.337 in both groups.

Various clinical outcomes were observed in the two groups. Neonatal Intensive care unit admission was needed in 10 percent of the neonates of the maternal hypothyroid group and in 2 percent of the neonates of the control group. There is no statistically significant difference for admission of neonatal intensice care unit in between the two groups (p=0.092).Among the maternal hypothyroidism group, out of 5 neonates of the maternal hypothyroid having NICU admission, the NICU stay was less than 2 days in 80 percent of the subjects while it was between 2 to 5 days in 20 percent of the subjects. Among the control group, only one neonate had ICU admission. The NICU stay for that one neonate was less than 2 days (1 day). Results obtained for NICU stay among the two study groups were statistically non significant (p=0.80). Among maternal hypothyroid group the Cord TSH of 100 percent neonates of were observed less than 20mIU/L and similarly in control study the Cord TSH was found less than 20mIU/L in 100 percent neonates. Neonatal cord TSH mean was 6.3 mIU/L among maternal hypothyroid group and 4.8 mIU/L among control group.The difference in cord TSH in two groups is statistically not significant (p value= 1).Major respiratory complication were seen in 10 percent of the patients of the maternal hypothyroid group and in 2 percent of the patients of the control group. There is no statistically significant difference observed in respiratory complications in two groups (p=0.092). Among 50 neonates in maternal hypothyroid group , neonatal jaundice was seen in 9 neonates contributing to 18% and 2 neonates were present in control group contributing to 4% . There were statistically significant difference in neonates having jaundice in maternal hypothyroid group as compared to control group (p=0.002).Among 50 neonates in maternal hypothyroid group requirement of phototherapy was needed in 9 neonates (18%) and in control group requirement was needed in 2 neonates contributing to 4%.There were statistically significant difference in neonates receiving phototherapy in maternal hypothyroid group as compared to control group(p=0.002).

Table 3: Clinical outcomes of neonates among the two groups

Untreated hypothyroidism during pregnancy poses significant risks to both the mother and the fetus. It has been associated with several adverse neonatal outcomes, including intrauterine growth restriction, low birth weight, preterm birth, prolonged neonatal jaundice, respiratory distress, delayed developmental milestones, neurodevelopmental delay, and intellectual disability. Given these risks, early clinical assessment of neonates born to hypothyroid mothers is crucial to identify any signs of hypothyroidism or related complications at the earliest possible stage. Multiple studies have established the link between maternal hypothyroidism and poor neonatal health outcomes.^9-13

 In this study , 70 percent of the patients of the maternal hypothyroid group and 72 percent of the patients of the control group were from urban residence In terms of residence, Chaitra K. et al14. observed that 64% of their study subjects were from urban areas, which is slightly lower than our findings. On the other hand, Kondhalkar A. et al15. reported that only 49.26% of their study participants were urban dwellers, suggesting geographical or institutional variation in the urban–rural distribution of hypothyroid pregnant women.

In this study, LSCS was the mode of delivery in majority of neonates ( 66%) born to mothers with hypothyroidism as compared to control group.This finding is consistent with several studies that have reported increased LSCS delivery rates among hypothyroid mothers. A study conducted by Nirmala et al¹⁶ in South India found that 51.3% of hypothyroid pregnant women underwent cesarean sections, compared to 28.2% in the control group. In this study, 82% of neonates born to hypothyroid mothers were delivered at term, while 6% were moderate preterm and 12% were late preterm. In contrast, among the control group, 96% of neonates were delivered at term, and only 4% were late preterm. The difference in gestational age at delivery between the two groups was found to be statistically significant.Similarly, Kiran et al. reported that among hypothyroid mothers, 0.2% of neonates were extremely preterm, 2.1% were very preterm, and 18.3% were late preterm, further supporting the association.¹⁷

In the present study, significant differences were observed in neonatal birth weight and anthropometric measurements between neonates born to hypothyroid mothers and those born to control group . Among the maternal hypothyroid group, 80% of the neonates were classified as appropriate for gestational age (AGA), while 20% were small for gestational age (SGA), In contrast, 100% of neonates in the control group were AGA, representing a statistically significant disparity. Similarly, Rashmi et al. found that 18.62% of neonates were SGA and 81.38% were AGA among hypothyroid pregnancies¹⁸. In the present study neonates born to maternal hypothyroid group are 30% low birthweight while remaining 70% are under normal birth weight as compared to control group where 2% are low birth weight and rest 98% are normal birth weight . These findings align with the results of Kiran et al., who reported that 21.5% of neonates born to hypothyroid mothers were LBW, and 77.3% were of appropriate weight.¹⁷ Juan Gui et al. observed that thyroid dysfunction during pregnancy was associated with a higher incidence of LBW.¹⁹

In addition to above , the mean length and head circumference , mean birth weight in the maternal hypothyroid group were 48.32 cm and 35.19 cm, 2.68 kg respectively, while in the control group, these measurements were 46.75 cm and 34.39 cm,2.92 kg respectively. The mean weight was statistically significant, further emphasizing the association between maternal hypothyroidism and reduced fetal growth. In our study difference between both groups in length and head circumference were statistically significant. Similarly, another showed no difference mean length but in contrary the same study showed significantly smaller head circumference in female neonates than male neonates born to maternal hypothyroid mothers.²⁰ In another study Trouva A et al showed higher maternal fT4 in early pregnancy was associated with a shorter birth length as well as lower birth weight is also observed.²¹

The analysis of gender distribution between neonates born to mothers with hypothyroidism and those in the control group revealed no statistically significant differences. In the maternal hypothyroid group, 56% of neonates were male and 44% were female, while in the control group, 48% were male and 52% were female. For instance, a study by Devi et al. reported a female- to-male ratio of 1:1.04 among neonates screened for hypothyroidism, with no significant association between maternal hypothyroidism and gender distribution.²²

NICU admission was needed in 10 percent of the neonates of the maternal hypothyroid group and in 2 percent of the neonates of the control group Kiran et al, in a similar study reported NICU admission in 12.1 percent neonates of the maternal hypothyroid mothers.¹⁷ A recent Finnish cohort study reported 14.4% NICU admissions in a population sample of 16,364 hypothyroid mothers.²³ Neonatal Respiratory complications were seen in 10 percent of the patients of the maternal hypothyroid group and in 2 percent of the patients of the control group. Similar to our study, Kiran et al reported respiratory complications seen in 8 percent of the neonates of maternal hypothyroid mothers.¹⁷ Männistö T et al reported RDS in 4 percent of the neonates born to hypothyroid mothers.²⁴ In the present study, neonatal jaundice requiring phototherapy was observed in 18% of neonates born to mothers with hypothyroidism, significantly higher than the incidence observed in the control group.In a study by Kiran et al., 14.8% of neonates born to hypothyroid mothers required phototherapy for hyperbilirubinemia, reinforcing the association between maternal thyroid status and increased bilirubin levels in neonates. Similarly, studies from South Asia like Singh et al , kumar et al , where neonatal jaundice is notably prevalent, have reported a baseline incidence ranging from 11% to 13% in the general population.^25,17,26

In conclusion, this study emphasizes the substantial impact of maternal hypothyroidism on neonatal health. Neonates born to hypothyroid mothers are at an increased risk for complications such as low birth weight , prolonged jaundice, respiratory distress, and growth abnormalities.Treated maternal hypothyroidism in pregnant mothers can significantly reduce complications compared to untreated cases. Timely diagnosis and treatment enable healthcare providers to manage thyroid hormone levels, minimizing risks to both mother and fetus. Therefore, effective management of hypothyroidism during pregnancy is crucial for optimal outcomes.

Acknowledgements: - none

Declarations: -

Funding: none

Conflict of interest: none

Ethical approval: approved by institutional ethical committee

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