What is the issue?
What are the effects of different screening methods (for example screening all women versus screening only some women, or not screening women) for thyroid dysfunction before or during pregnancy on outcomes for the mother and her baby?
Why is this important?
The thyroid is a large gland in the neck that produces hormones that help to regulate the chemical processes in the body that maintain life, including growth and energy use. If a woman has an overactive thyroid (hyperthyroidism), or an underactive thyroid (hypothyroidism) in pregnancy which is not managed, there is a possibility of poor outcomes for the mother and her baby. The mother may be more likely to develop high blood pressure and protein in the urine (pre-eclampsia), give birth before 37 weeks of gestation (preterm birth), and her baby may develop disabilities (such as cerebral palsy, blindness, deafness and other developmental delays including intellectual impairment). Managing thyroid dysfunction in pregnancy (e.g. thyroxine for hypothyroidism, or antithyroid medication for hyperthyroidism) may improve outcomes for mothers and their babies. There are different methods of screening for thyroid dysfunction, including case finding, which means screening only pregnant women who are thought to be at high risk of thyroid dysfunction, or universal screening, which involves screening all pregnant women. Although universal screening may help to diagnose more women with hyperthyroidism or hypothyroidism than case finding, it could also lead to more women having medications and may be costly. It is not currently clear what the effects are of these different methods of screening for thyroid dysfunction for the mother and her baby, and health services.
What evidence did we find?
In our search of the medical literature we found two randomised controlled trials, involving 26,408 women. The quality of the included trials was high, and the quality of the evidence they provided was moderate to high.
(1) Universal screening for thyroid dysfunction in pregnancy, and hypothyroidism specifically, increased the number of women diagnosed with hypothyroidism, who were subsequently treated (one trial involving 4562 women; and one trial involving 21,839 women). The study of 4562 women also showed that there may have been an increase in the number of women diagnosed with hyperthyroidism with universal screening.
(2) Universal screening and subsequent treatment did not show clear benefits or harms for the women or their babies as it did not change the number of women with pre-eclampsia (in the one trial involving 4516 of 4562 women for this outcome), the number of women who gave birth preterm (one trial involving 4516 women), or the number of children with a disability (an intelligence quotient (IQ) less than 85 at three years of age) (one trial involving 794 children whose mothers had hypothyroidism from the total of 21,839 women).
(3) One of the included trials did not report on later disabilities for the baby, and the other trial did not report on pre-eclampsia or preterm birth. Neither of the trials reported on use of health services or costs.
What does this mean?
Although the overall quality of the evidence was moderate to high, apart from finding that universal screening can help to diagnose more women with hypothyroidism (who may then be treated), there were no clear differences in outcomes for the mothers and their babies between universal screening and case finding (or not screening at all). Even though the two included studies involved a large number of women, further evidence is needed to assess the potential short- and long-term benefits or harms of different screening methods, along with the impact on health services including costs.
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.
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.
To assess the effects of different screening methods (and subsequent management) for thyroid dysfunction pre-pregnancy and during pregnancy on maternal and infant outcomes.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (14 July 2015) and reference lists of retrieved studies.
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.
Two review authors independently assessed eligibility of studies, extracted and checked data accuracy, and assessed the risk of bias of included studies.
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 dysfunction
One 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 hypothyroidism
One 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.