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Neonatal Thyrotropin as Measured in a Congenital Hypothyroidism Screening Program: Influence of the Mode of Delivery

Department of Endocrinology (A.M.), Royal North Shore Hospital, St. Leonards 2065, Australia; Evidence for Population Health Unit (P.M.), University of Manchester, Manchester M13 9PT, United Kingdom; New South Wales Biochemical Genetics and Newborn Screening Services (V.W., B.W.), The Children’s Hospital at Westmead, Sydney 2145, Australia; and Discipline of Paediatrics (B.W.), University of Sydney, Sydney 2050, Australia

Address all correspondence and requests for reprints to: Aidan McElduff, Department of Endocrinology, Royal North Shore Hospital, St. Leonards 2065, Australia. E-mail: aidanm{at}med.usyd.edu.au.

	Abstract

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Context: Many developed countries are reexperiencing iodine deficiency. One World Health Organization index of iodine deficiency in populations is the percentage of neonates with TSH levels greater than 5 mIU/liter 72 h after delivery. Measured TSH levels vary with methodology and are influenced by external factors including iodine exposure at time of delivery.

Objective: We wished to determine whether babies delivered by cesarean section have higher levels of TSH than babies delivered vaginally because this factor could influence determination of iodine deficiency.

Design and Setting: This was a cohort study of mothers delivering at a teaching hospital in 2002–2003 and their babies.

Patients and Methods: Women delivering a live infant were eligible for the study. Demographic data, mode of delivery, and subsequent routine newborn screening TSH levels were recorded.

Results: Of 2031 infants, 31.2% were delivered by cesarean section; 1864 babies were born after 37 wk, with blood samples collected by d 5 (>91% on d 3). Significant predictors of TSH concentration were the day TSH was measured and type of delivery. The distribution curve of TSH values was right shifted in infants born by cesarean section. The percentage of neonates born by cesarean with at TSH value greater than 5 was 7.1%. The figure for those born vaginally was 4.3%.

Conclusions: Babies delivered by cesarean section are significantly more likely to have TSH levels greater than 5 mIU/liter on d 3 than those delivered vaginally. With the rise in the rate of births by cesarean, this could be an important factor in assessing population iodine deficiency using neonatal TSH levels.

	Introduction

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IODINE DEFICIENCY REMAINS the most common cause of intellectual disability in the world (1). Australia (2, 3, 4), like many countries in the developed world, is reexperiencing iodine deficiency (2). Public health measures including iodine supplementation are required to protect many populations from the devastating effects of iodine deficiency on fetal and neonatal brain development (5). An important part of any supplementation program is ongoing monitoring of the effectiveness of the program (4). One World Health Organization (WHO)-approved method of monitoring the effectiveness of iodine supplementation at a population level is the determination of the percentage of neonates with a TSH value greater than 5 mIU/liter (whole blood), 72 h after delivery. A population is considered iodine replete if less than 3% have a TSH value greater than 5 mIU/liter (6). Neonatal TSH screening programs allow for population monitoring of iodine status according to the previously mentioned criterion. To fulfill the criteria, TSH screening would require standardization and the factors affecting neonatal TSH as measured in the congenital hypothyroidism screening programs would need to be understood.

We previously found that infants born by cesarean section had higher TSH values postpartum than those delivered vaginally (7). This difference was not significant, but the number studied was small (n = 49). One plausible mechanism to explain this potential effect is that topical iodine skin preparation for cesarean section delivers an iodine load to the mother, part of which is transferred to the infant resulting in acute inhibition of thyroid function (Wolff-Chaikoff effect).

The aim of this study was to determine the effect of mode of delivery, cesarean section or vaginal, on neonatal TSH at both an individual and population level. Specifically we wished to determine whether cesarean section raised TSH values to a level that may suggest neonatal hypothyroidism for the individual and/or whether cesarean section altered the distribution of the population TSH values that could lead to difficulties in interpreting a population’s iodine status. The study was part of a series examining the iodine status of our local population (2, 7, 8).

	Patients and Methods

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Patient data

Women who delivered a live infant at Royal North Shore Hospital in 2002 or 2003 were identified on the local obstetric database. The names, hospital identification numbers, and date of delivery were obtained. This information was matched to infants in the newborn screening database using hospital of birth, name, and date of birth. Neonatal TSH and the date of collection were added to the file. Individual discrepancies were resolved by direct examination of the mothers’ and/or infants’ local records. The combined data were then returned to the obstetric database for rechecking and the addition of data including maternal parity, gestational age, neonatal weight, fetal sex, and delivery order for twins.

Newborn screening TSH assay

All babies in New South Wales have a heel-prick blood sample collected at least 48 h after birth, usually on d 3, as part of the routine newborn screening program. The samples are sent to the central New South Wales Newborn Screening Laboratory, at which TSH (whole blood) is measured by dissociation-enhanced fluoroimmunoassay performed on an auto-DELFIA analyzer (PerkinElmer, Rowville, Victoria, Australia). The between-assay coefficient of variation at 5 mIU/liter was 10%. The lowest standard used was 1 mIU/liter.

Age definition

The Newborn Screening Service aims for samples more than 48 h after birth and has a policy of not accepting samples collected before this time point. In this paper day means calendar day after delivery (and does not imply a set number of hours.)

The study was approved by the institutional ethics committees.

	Results

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Information on 2031 infants was available. There were 110 infants from multiple births. Most (2000) samples had been collected on d 2–4 with 1859 of these collected on d 3. Six hundred fifty-one women (32.1%) were delivered by cesarean section. Samples were collected on d 3 in 91.7% for babies born by cesarean section and in 91.2% of babies who were delivered vaginally. Babies who were delivered by cesarean section were more likely to have been delivered earlier than babies delivered by vaginal delivery (P < 0.001); more specifically more babies delivered by cesarean section were born before 37 wk, 10.8% vs. 6.3% for vaginal delivery (P < 0.001). The mean TSH value was higher in the cesarean section group (2.20 vs. 1.97 mIU/liter P = 0.040).

We performed a multiple linear regression using only the data on those babies (n = 1864) who were born after 37 wk (term) and whose TSH was measured before d 6. The outcome variable in the analysis was the TSH and the results are shown in Table 1. Significant predictors of the TSH concentration were the day TSH was measured and type of delivery. TSH tended to fall from the day of delivery, leveling off on d 2, and TSH levels were higher in neonates born by cesarean section. There were disparate effects of birth weight and gestational age. Lower TSH was associated with greater birth weight, whereas higher TSH values were associated with older gestational age.

View larger version (11K): [in this window] [in a new window]   FIG. 1. The distribution of TSH values (in milliinternational units per liter) according to mode of delivery from samples collected on d 3 only.

	Discussion

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These data demonstrate that distribution of neonatal TSH concentrations varies subtly according to the mode of delivery. Cesarean section is associated with a shift to the right (Fig. 1). We assume that this effect is related to the topical iodine used to prepare for cesarean section in our hospital, although we have not confirmed that in this study. A previous small study (7) revealed higher urine and breast milk iodine concentrations in mothers who underwent cesarean section. The neonatal TSH in that study was positively correlated with breast milk iodine concentration, consistent with the postulate that the iodine load to the mother was, in part, transferred to the newborn both before and after delivery and that this iodine load was responsible for the rise in neonatal TSH. We have no iodine measurements in this report. A similar but more marked elevation in neonatal TSH has been documented with topical iodine antiseptic use on the neonate in some (9, 10, 11, 12, 13) but not all reports (14, 15). It is likely many factors contribute to the variation in outcome between these reports. One factor may be that the change in TSH concentration induced by topical iodine in any individual is small and likely to go undetected in that individual unless other factors likely to cause hypothyroidism are present. We needed a large number of subjects to detect a small but significant shift in the group data. The small increase in TSH in the cesarean group moves the distribution curve of neonatal TSH values to the right, compared with TSH values of neonates born vaginally (Fig. 1). The effect of cesarean on the distribution is significant (Table 1). This effect would have to be taken into account, or adjusted for, if the congenital screening programs were ever adapted for surveillance of the population’s iodine status.

A report from Poland (16) found significant variations in the percentage of TSH values greater than 5 mIU/liter between hospitals that did or did not use topical iodine in their obstetric clinics. This supports our findings in general, although we have identified a specific event, preparation for cesarean section, which in our population appears to be a particular risk factor for an elevated neonatal TSH concentration.

Two studies (17, 18) reported higher cord blood TSH concentrations in infants born vaginally, although Miyamoto et al. (18) reported that this did not persist to interfere with congenital hypothyroidism screening. Gruneiro-Papendieck et al. (19) reported on the need to use samples collected from infants after 48 h and highlighted the WHO silence on the methodology used to measure TSH.

Our findings demonstrate only one factor that needs to be taken into account when applying the WHO recommendations to assessment of population iodine status. Other important factors include the method of TSH measurement, the age at sampling, and the percentage of low-birth-weight babies. However, with the rise in the rate of births by cesarean section and the variability of this percentage from area to area, this will be an important factor.

	Footnotes

 
First Published Online September 6, 2005

Abbreviation: CI, Confidence interval.

Received April 11, 2005.

Accepted August 31, 2005.

	References

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