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Meta-Analysis
. 2015 Sep 21;2015(9):CD011263.
doi: 10.1002/14651858.CD011263.pub2.

Screening and subsequent management for thyroid dysfunction pre-pregnancy and during pregnancy for improving maternal and infant health

Laura Spencer  1 , Tanya Bubner, Emily Bain, Philippa Middleton
Affiliations
Meta-Analysis

Screening and subsequent management for thyroid dysfunction pre-pregnancy and during pregnancy for improving maternal and infant health

Laura Spencer et al. Cochrane Database Syst Rev. .

Abstract

Background: Thyroid dysfunction pre-pregnancy and during pregnancy (both hyper- and hypothyroidism) is associated with increased risk of adverse outcomes for mothers and infants in the short- and long-term. Managing the thyroid dysfunction (e.g. thyroxine for hypothyroidism, or antithyroid medication for hyperthyroidism) may improve outcomes. The best method of screening to identify and subsequently manage thyroid dysfunction pre-pregnancy and during pregnancy is unknown.

Objectives: To assess the effects of different screening methods (and subsequent management) for thyroid dysfunction pre-pregnancy and during pregnancy on maternal and infant outcomes.

Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (14 July 2015) and reference lists of retrieved studies.

Selection criteria: Randomised or quasi-randomised controlled trials, comparing any screening method (e.g. tool, program, guideline/protocol) for detecting thyroid dysfunction (including hypothyroidism, hyperthyroidism, and/or thyroid autoimmunity) pre-pregnancy or during pregnancy with no screening, or alternative screening methods.

Data collection and analysis: Two review authors independently assessed eligibility of studies, extracted and checked data accuracy, and assessed the risk of bias of included studies.

Main results: We included two randomised controlled trials (involving 26,408 women) - these trials were considered to be at low risk of bias. Universal screening (screening all women) versus case finding (screening only those at perceived increased risk) in pregnancy for thyroid dysfunctionOne trial (4562 women) compared universal screening with case finding for thyroid dysfunction. Before 11 weeks' gestation, women in the universal screening group, and 'high-risk' women in the case finding group had their sera tested for TSH (thyroid stimulating hormone), fT4 (free thyroxine) and TPO-Ab (thyroid peroxidase antibody); women with hypothyroidism (TSH > 2.5 mIU/litre) received levothyroxine; women with hyperthyroidism (undetectable TSH and elevated fT4) received antithyroid medication.In regards to this review's primary outcomes, compared with the case finding group, more women in the universal screening group were diagnosed with hypothyroidism (risk ratio (RR) 3.15, 95% confidence interval (CI) 1.91 to 5.20; 4562 women; GRADE: high quality evidence), with a trend towards more women being diagnosed with hyperthyroidism (RR 4.50, 95% CI 0.97 to 20.82; 4562 women; P = 0.05; GRADE: moderate quality evidence). No clear differences were seen in the risks of pre-eclampsia (RR 0.87, 95% CI 0.64 to 1.18; 4516 women; GRADE: moderate quality evidence), or preterm birth (RR 0.99, 95% CI 0.80 to 1.24; 4516 women; GRADE: high quality evidence) between groups. This trial did not report on neurosensory disability for the infant as a child.Considering this review's secondary outcomes, more women in the universal screening group received pharmacological treatment for thyroid dysfunction (RR 3.15, 95% CI 1.91 to 5.20; 4562 women). No clear differences between groups were observed for miscarriage (RR 0.90, 95% CI 0.68 to 1.19; 4516 women; GRADE: moderate quality evidence), fetal and neonatal death (RR 0.92, 95% CI 0.42 to 2.02; 4516 infants; GRADE: moderate quality evidence), or other secondary outcomes: pregnancy-induced hypertension, gestational diabetes, congestive heart failure, thyroid storm, mode of birth (caesarean section), preterm labour, placental abruption, respiratory distress syndrome, low birthweight, neonatal intensive care unit admission, or other congenital malformations. The trial did not report on a number of outcomes including adverse effects associated with the intervention. Universal screening versus no screening in pregnancy for hypothyroidismOne trial (21,846 women) compared universal screening with no screening for hypothyroidism. Before 15 + 6 weeks' gestation, women in the universal screening group had their sera tested; women who screened 'positive' (TSH > 97.5th percentile, fT4 < 2.5th percentile, or both) received levothyroxine.Considering primary review outcomes, compared with the no screening group, more women in the universal screening screened 'positive' for hypothyroidism (RR 998.18, 95% CI 62.36 to 15,978.48; 21,839 women; GRADE: high quality evidence). No data were provided for the outcome pre-eclampsia, and for preterm birth, the trial reported rates of 5.6% and 7.9% for the screening and no screening groups respectively (it was unclear if these percentages related to the entire cohort or women who screened positive). No clear difference was seen for neurosensory disability for the infant as a child (three-year follow-up IQ score < 85) (RR 0.85, 95% CI 0.60 to 1.22; 794 infants; GRADE: moderate quality evidence).More women in the universal screening group received pharmacological treatment for thyroid dysfunction (RR 1102.90, 95% CI 69.07 to 17,610.46; 1050 women); 10% had their dose lowered because of low TSH, high fT4 or minor side effects. No clear differences were observed for other secondary outcomes, including developmental delay/intellectual impairment at three years. Most of our secondary outcomes, including miscarriage, fetal or neonatal death were not reported.

Authors' conclusions: Based on the existing evidence, though universal screening for thyroid dysfunction in pregnancy increases the number of women diagnosed with hypothyroidism who can be subsequently treated, it does not clearly impact (benefit or harm) maternal and infant outcomes.While universal screening versus case finding for thyroid dysfunction increased diagnosis and subsequent treatment, we found no clear differences for the primary outcomes: pre-eclampsia or preterm birth. No clear differences were seen for secondary outcomes, including miscarriage and fetal or neonatal death; data were lacking for the primary outcome: neurosensory disability for the infant as a child, and for many secondary outcomes. Though universal screening versus no screening for hypothyroidism similarly increased diagnosis and subsequent treatment, no clear difference was seen for the primary outcome: neurosensory disability for the infant as a child (IQ < 85 at three years); data were lacking for the other primary outcomes: pre-eclampsia and preterm birth, and for the majority of secondary outcomes.For outcomes assessed using the GRADE approach the evidence was considered to be moderate or high quality, with any downgrading of the evidence based on the presence of wide confidence intervals crossing the line of no effect.More evidence is needed to assess the benefits or harms of different screening methods for thyroid dysfunction in pregnancy, on maternal, infant and child health outcomes. Future trials should assess impacts on use of health services and costs, and be adequately powered to evaluate the effects on short- and long-term outcomes.

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Conflict of interest statement

Laura Spencer: None known.

Tanya Bubner: None known.

Emily Bain: None known.

Philippa Middleton: None known.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 1 Thyroid dysfunction diagnosed in pregnancy: hypothyroid.
1.2
1.2. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 2 Thyroid dysfunction diagnosed in pregnancy: hyperthyroid.
1.3
1.3. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 3 Thyroid dysfunction diagnosed in pregnancy: hypothyroid (subgroups based on baseline risk).
1.4
1.4. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 4 Thyroid dysfunction diagnosed in pregnancy: hyperthyroid (subgroups based on baseline risk).
1.5
1.5. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 5 Pre‐eclampsia.
1.6
1.6. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 6 Pre‐eclampsia (subgroups based on baseline risk and thyroid status).
1.7
1.7. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 7 Preterm birth.
1.8
1.8. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 8 Preterm birth (subgroups based on baseline risk and thyroid status).
1.9
1.9. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 9 Pharmacological treatment for thyroid dysfunction: thyroxine for hypothyroidism.
1.10
1.10. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 10 Miscarriage.
1.11
1.11. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 11 Pregnancy‐induced hypertension.
1.12
1.12. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 12 Gestational diabetes.
1.13
1.13. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 13 Congestive heart failure.
1.14
1.14. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 14 Thyroid storm.
1.15
1.15. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 15 Mode of birth: caesarean.
1.16
1.16. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 16 Preterm labour.
1.17
1.17. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 17 Placental abruption.
1.18
1.18. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 18 Fetal and neonatal death.
1.19
1.19. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 19 Respiratory distress syndrome.
1.20
1.20. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 20 Low birthweight.
1.21
1.21. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 21 Neonatal intensive care unit admission.
1.22
1.22. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 22 Other congenital malformations.
1.23
1.23. Analysis
Comparison 1 Universal screening versus case finding in pregnancy for any thyroid dysfunction, Outcome 23 At least one adverse outcome.
2.1
2.1. Analysis
Comparison 2 Universal screening versus no screening in pregnancy for hypothyroidism, Outcome 1 Thyroid dysfunction diagnosed in pregnancy: Hypothyroid.
2.2
2.2. Analysis
Comparison 2 Universal screening versus no screening in pregnancy for hypothyroidism, Outcome 2 Neurosensory disability (any of cerebral palsy, blindness, deafness, developmental delay/intellectual impairment, at latest time reported): IQ < 85 at 3 years of age.
2.3
2.3. Analysis
Comparison 2 Universal screening versus no screening in pregnancy for hypothyroidism, Outcome 3 Neurosensory disability (any of cerebral palsy, blindness, deafness, developmental delay/intellectual impairment, at latest time reported): IQ Z‐score < 1 at 3 years of age.
2.4
2.4. Analysis
Comparison 2 Universal screening versus no screening in pregnancy for hypothyroidism, Outcome 4 Pharmacological treatment for thyroid dysfunction: thyroxine for hypothyroidism.
2.5
2.5. Analysis
Comparison 2 Universal screening versus no screening in pregnancy for hypothyroidism, Outcome 5 Developmental delay/intellectual impairment: Mean standardised IQ at 3 years of age.
2.6
2.6. Analysis
Comparison 2 Universal screening versus no screening in pregnancy for hypothyroidism, Outcome 6 Developmental delay/intellectual impairment: Mean IQ Z‐score at 3 years of age.
2.7
2.7. Analysis
Comparison 2 Universal screening versus no screening in pregnancy for hypothyroidism, Outcome 7 Developmental delay/intellectual impairment: Mean CBCL T‐score at 3 years of age.
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Update of

  • doi: 10.1002/14651858.CD011263

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Publication types