Maternal thyroid function during early pregnancy and cognitive functioning in early childhood: the generation R study.
BACKGROUND
Thyroid hormones are essential for neurodevelopment from early pregnancy onward. Yet population-based data on the association between maternal thyroid function in early pregnancy and children's cognitive development are sparse.


OBJECTIVE
Our objective was to study associations of maternal hypothyroxinemia and of early pregnancy maternal TSH and free T(4)(FT(4)) levels across the entire range with cognitive functioning in early childhood.


METHODS
We conducted a population-based cohort in The Netherlands.


METHODS
Participants included 3659 children and their mothers.


METHODS
In pregnant women with normal TSH levels at 13 wk gestation (SD = 1.7), mild and severe maternal hypothyroxinemia were defined as FT(4) concentrations below the 10th and 5th percentile, respectively. Children's expressive vocabulary at 18 months was reported by mothers using the MacArthur Communicative Development Inventory. At 30 months, mothers completed the Language Development Survey and the Parent Report of Children's Abilities measuring verbal and nonverbal cognitive functioning.


RESULTS
Maternal TSH was not related to the cognitive outcomes. An increase in maternal FT(4) predicted a lower risk of expressive language delay at 30 months only. However, both mild and severe maternal hypothyroxinemia was associated with a higher risk of expressive language delay across all ages [odds ratio (OR) = 1.44; 95% confidence interval (CI) = 1.09-1.91; P = 0.010 and OR = 1.80; 95% CI = 1.24-2.61; P = 0.002, respectively]. Severe maternal hypothyroxinemia also predicted a higher risk of nonverbal cognitive delay (OR = 2.03; 95% CI = 1.22-3.39; P = 0.007).


CONCLUSIONS
Maternal hypothyroxinemia is a risk factor for cognitive delay in early childhood.
The Generation R Study, Erasmus Medical University Center, 3000 DR Rotterdam, The Netherlands.
Jens
J
Henrichs
Jacoba J
JJ
Bongers-Schokking
Jacqueline J
JJ
Schenk
Akhgar
A
Ghassabian
Henk G
HG
Schmidt
Theo J
TJ
Visser
Herbert
H
Hooijkaas
Sabine M P F
SM
de Muinck Keizer-Schrama
Albert
A
Hofman
Vincent V W
VV
Jaddoe
Willy
W
Visser
Eric A P
EA
Steegers
Frank C
FC
Verhulst
Yolanda B
YB
de Rijke
Henning
H
Tiemeier
D000328:Adult; D002648:Child; D002657:Child Development / Q000502:physiology*; D003071:Cognition / Q000502:physiology*; D015331:Cohort Studies; D002658:Developmental Disabilities / Q000097:blood / Q000209:etiology; D005191:Family Characteristics; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000150:complications / Q000503:physiopathology; D033261:Maternal-Fetal Relations; D009035:Mothers; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood / Q000502:physiology*; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000503:physiopathology; D012307:Risk Factors; D013960:Thyroid Function Tests; D013961:Thyroid Gland / Q000502:physiology*; D013972:Thyrotropin / Q000097:blood
D013972:Thyrotropin