Association between Thyroid Function and Respiratory Distress Syndrome in Preterm Infants
Round 1
Reviewer 1 Report
The manuscript “Association between thyroid function and respiratory distress syndrome in preterm infants” offers an exhaustive analysis of the relationship between the clinical spectrum of this syndrome and the influence of thyroid hormones in it.
The study includes a significant sample size to make comparisons, allowing to identify and eliminate confounding factors, what offers a sound analysis of this association. Methods have been explained in detail and thyroid hormones have been analyzed in fixed moments (birth, 1, 3 and 6 weeks after birth). Additionally, the discussion is very well written, and findings have been commented and placed in context.
I only have two minor comments to make:
a) Figure 3 is labeled as figure 2.
b) Lines 133-136 are not related to this work.
Author Response
thank you for your review and response.
a)Figure 3 is labeled as figure 2.
→ Figure 4 is corrected as Figure 3.
b)Lines 133-136 are not related to this work.
→ We deleted the lines
Sincerely yours.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Thank you for the opportunity to review this paper.
In this report the authors have investigated the relationship between neonatal thyroid status and the risk of respiratory distress syndrome in preterm infants. This is an interesting topic. Thyroid hormones are known to influence lung maturation and surfactant synthesis and the authors duly discuss and cite previous publications in this topic.
I think the report is potentially interesting to a clinical leadership but the content and presentation needs to improve to be clear and understandable. I hope the authors find the following specific comments useful:
Abstract:
"fT4 was higher in the control group on the day of 17 birth but not significantly so. " - If the change was not significant I do not think this needs to be mentioned, particularly not in the abstract.
Introduction:
Well written and balanced
Methods:
" RDS was defined as those infants who required surfactant administration on the day 63 of birth." - This is a pragmatic definition but then please define what was the guideline to give surfactant.
Results:
Line 108: "There were no differences between the groups accord- 108 ing to gestational age, maternal age, gestational diabetes mellitus, pathological chorioam- 109 nionitis, maternal thyroid disease, or antenatal steroid exposure." - As the intergroup comparison here was based on gestational age, it is not surprising that there was no difference here between the gestational age...
Line 112: " However, the levels in the RDS group 112 were significantly lower than those in the control group (0.39 ± 0.18 vs. 0.49 ± 0.12, p < 113 0.001)" - Please state at which postnatal age. Also, this is nit surprising, as babies with RDS were more preterm. Please discuss.
Line 115: "The TSH level of the RDS 115 group was significantly lower than that of the control group at birth and at 3 weeks (p = 116 0.048, p = 0.002), but there was no significant difference at either 1 or 6 weeks after birth." - This is not what the Figure shows. On Figure 2, the TSH is actually signficantly higher (p=-.002) in the RDS group at 3 weeks of age. Please correct and explain.
Figure 2 Legend: "hyroid stimulating hormone levels were higher in the RDS group at birth, birth, fT4 was significantly lower in the RDS group. (C) Thyroid stimulating hormone levels were higher in the RDS group at birth, but there was no significant difference 1 week after birth. but there was no significant difference 1 week after birth" - Again this is not what the figure shows (see above), please correct and explain.
- Figure 3 (which is incorrectly labeled as Figure 2). This Figure is not understandable to this reviewer. What the Figure should demonstrate is that in a multiple logistic regression model, TSH is level is an independent risk factor for RDS even when gestation and weight and apgar score (which were different between the groups) are taken into account. However, I cannot interpret this Figure.
Discussion: Balanced and comprehensive.
Author Response
Dear. reviewer
We thank you for your time and consideration on our submission.
According to reviewer’s comments, we have corrected our paper.
I look forward to hearing from you
Sincerely,
- Abstract:
"fT4 was higher in the control group on the day of 17 birth but not significantly so. " - If the change was not significant I do not think this needs to be mentioned, particularly not in the abstract.
→ we deleted that phrase.
- Methods:
" RDS was defined as those infants who required surfactant administration on the day 63 of birth." - This is a pragmatic definition but then please define what was the guideline to give surfactant.
→ In many groups, that definitions is used extensively. Because As it may be pragmatic, We edited it following that
RDS was defined as those infants with air-bronchograms on chest x-ray and respira-tory distress symptoms including chest retractions, nasal flaring, and at least a 40% FiO2 requirement..
Results:
- Line 108: "There were no differences between the groups accord- 108 ing to gestational age, maternal age, gestational diabetes mellitus, pathological chorioam- 109 nionitis, maternal thyroid disease, or antenatal steroid exposure." - As the intergroup comparison here was based on gestational age, it is not surprising that there was no difference here between the gestational age...
→ we deleted that pharse.
- Line 112: " However, the levels in the RDS group 112 were significantly lower than those in the control group (0.39 ± 0.18 vs. 0.49 ± 0.12, p < 113 0.001)" - Please state at which postnatal age. Also, this is nit surprising, as babies with RDS were more preterm. Please discuss.
→ We edited it following that
→ “However, the T3 levels of RDS group at every time point was significantly lower (0.39 ± 0.2 vs 0.49 ± 0.1 at birth; 0.71 ± 0.3 vs 0.94 ± 0.2 at PNA 1 weeks; 0.83 ± 0.3 vs 1.10 ± 0.2 at PNA 3 weeks; 1.02 ± 0.3 vs. 1.24 ± 0.3 at PNA 6 weeks; p < 0.001).”
- Line 115: "The TSH level of the RDS 115 group was significantly lower than that of the control group at birth and at 3 weeks (p = 116 0.048, p = 0.002), but there was no significant difference at either 1 or 6 weeks after birth." - This is not what the Figure shows. On Figure 2, the TSH is actually signficantly higher (p=-.002) in the RDS group at PNA 3 weeks of age. Please correct and explain.
→ We corrected it following that
“The TSH levels of the RDS group were significantly lower than that of the control group at birth (p = 0.048), and TSH level of the RDS group was increased gradationally. At PNA 3 weeks, levels in the RDS group were significantly higher than that in the control goup (p = 0.002).”
- Figure 2 Legend: "hyroid stimulating hormone levels were higher in the RDS group at birth, birth, fT4 was significantly lower in the RDS group. (C) Thyroid stimulating hormone levels were higher in the RDS group at birth, but there was no significant difference 1 week after birth. but there was no significant difference 1 week after birth" - Again this is not what the figure shows (see above), please correct and explain.
→ We corrected it following that
Figure 2. Thyroid hormone levels by postnatal age.
(A) Triiodothyronine (T3) levels increased up to 6 weeks after birth. T3 levels were lower in the RDS groups on the day of birth and 1, 3, and 6 weeks after birth. (B) Free thyroxine (fT4) was higher, but not significantly so, in the control group at birth. One week after birth, fT4 was significantly lower in the RDS groups. (C) Thyroid stimulating hormone levels were lower in the RDS groups at birth, but there was no significant difference at 1 week after birth.
- Figure 3 (which is incorrectly labeled as Figure 2). This Figure is not understandable to this reviewer. What the Figure should demonstrate is that in a multiple logistic regression model, TSH is level is an independent risk factor for RDS even when gestation and weight and apgar score (which were different between the groups) are taken into account. However, I cannot interpret this Figure.
→ We corrected it following that
Figure 3.
Adjusted odds ratio and their 95% confidence intervals for RDS after multivariate logistic regression analysis adjusted with confounders.
Effect of TSH and T3 at birth (A) and TSH and T3 at PNA 3 weeks
CI, confidence interval; OR, Odds ratio; T3, Triiodothyronine; TSH, Thyroid stimulating hormone; PNA, Postnatalage
Author Response File: Author Response.pdf
Round 2
Reviewer 2 Report
Thanks for answering my questions and addressing my concerns.
