Gestational thyrotoxicosis, antithyroid drug use and neonatal outcomes within an integrated healthcare delivery system.
BACKGROUND
Increasing attention has focused on the prevalence and outcomes of hyperthyroidism in pregnancy, given concerns for hepatotoxicity and embryopathy associated with antithyroid drugs (ATDs).


METHODS
In an integrated health care delivery system, we examined the prevalence of thyrotoxicosis and gestational ATD use (propylthiouracil [PTU] or methimazole [MMI]) in women with delivered pregnancies from 1996 to 2010. Birth outcomes were compared among all infants and those born to mothers with diagnosed thyrotoxicosis or ATD therapy during gestation, with examination of ATD-associated hepatotoxicity and congenital malformations in the latter subgroups.


RESULTS
Among 453,586 mother-infant pairs (maternal age 29.7±6.0 years, 57.1% nonwhite), 3.77 per 1000 women had diagnosed thyrotoxicosis and 1.29 per 1000 had gestational ATD exposure (86.5% PTU, 5.1% MMI, 8.4% both). Maternal PTU-associated hepatotoxicity occurred with a frequency of 1.80 per 1000 pregnancies. Infants of mothers with diagnosed thyrotoxicosis (odds ratio [OR] 1.28, 95% confidence interval [CI 1.05-1.55]) or gestational ATD use (OR 1.31 [1.00-1.72]) had an increased risk of preterm birth compared to those born to mothers without thyrotoxicosis or ATD. The risk of neonatal intensive care unit (NICU) admission was also higher with maternal thyrotoxicosis (OR 1.30 [1.07-1.59]) and ATD exposure (OR 1.64 [CI 1.26-2.13]), adjusting for prematurity. Congenital malformation rates were low and similar among infants born to mothers with thyrotoxicosis or ATD exposure (30-44 per 1000 infants).


CONCLUSIONS
Gestational ATD exposure occurred in 1.29 per 1000 mother-infant pairs while a much larger number had maternal diagnosed thyrotoxicosis but no drug exposure during pregnancy. Infants of mothers with gestational ATD use or diagnosed thyrotoxicosis were more likely to be preterm and admitted to the NICU. The rates of congenital malformation were low for mothers diagnosed with thyrotoxicosis and did not differ by ATD use. Among women with gestational PTU therapy, the frequency of PTU-associated hepatotoxicity was 1.8 per 1000 delivered pregnancies. These findings from a large, population-based cohort provide generalizable estimates of maternal and infant risks associated with maternal thyrotoxicosis and related pharmacotherapy.
1Division of Research, Kaiser Permanente Northern California, Oakland, California.|2Division of Endocrinology, Department of Medicine, Kaiser Permanente Oakland Medical Center, Oakland, California.
Joan C
JC
Lo
3Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida.
Scott A
SA
Rivkees
1Division of Research, Kaiser Permanente Northern California, Oakland, California.
Malini
M
Chandra
1Division of Research, Kaiser Permanente Northern California, Oakland, California.
Joel R
JR
Gonzalez
4Department of Health Studies, Westat, Rockville, Maryland.
James J
JJ
Korelitz
1Division of Research, Kaiser Permanente Northern California, Oakland, California.|5Department of Inpatient Pediatrics, Kaiser Permanente Oakland Medical Center, Oakland, California.
Michael W
MW
Kuzniewicz
D000328:Adult; D013956:Antithyroid Agents / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology* / Q000209:etiology; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000453:epidemiology*; D019033:Delivery of Health Care, Integrated; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal / Q000706:statistics & numerical data; D008713:Methimazole / Q000627:therapeutic use; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D047928:Premature Birth / Q000453:epidemiology*; D015995:Prevalence; D011441:Propylthiouracil / Q000009:adverse effects / Q000627:therapeutic use; D013971:Thyrotoxicosis / Q000188:drug therapy* / Q000453:epidemiology; D055815:Young Adult
D013956:Antithyroid Agents; D008713:Methimazole; D011441:Propylthiouracil