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Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy.

Abstract Background Subclinical thyroid disease during pregnancy may be associated with adverse outcomes, including a lower-than-normal IQ in offspring. It is unknown whether levothyroxine treatment of women who are identified as having subclinical hypothyroidism or hypothyroxinemia during pregnancy improves cognitive function in their children. Methods We screened women with a singleton pregnancy before 20 weeks of gestation for subclinical hypothyroidism, defined as a thyrotropin level of 4.00 mU or more per liter and a normal free thyroxine (T4) level (0.86 to 1.90 ng per deciliter [11 to 24 pmol per liter]), and for hypothyroxinemia, defined as a normal thyrotropin level (0.08 to 3.99 mU per liter) and a low free T4 level (<0.86 ng per deciliter). In separate trials for the two conditions, women were randomly assigned to receive levothyroxine or placebo. Thyroid function was assessed monthly, and the levothyroxine dose was adjusted to attain a normal thyrotropin or free T4 level (depending on the trial), with sham adjustments for placebo. Children underwent annual developmental and behavioral testing for 5 years. The primary outcome was the IQ score at 5 years of age (or at 3 years of age if the 5-year examination was missing) or death at an age of less than 3 years. Results A total of 677 women with subclinical hypothyroidism underwent randomization at a mean of 16.7 weeks of gestation, and 526 with hypothyroxinemia at a mean of 17.8 weeks of gestation. In the subclinical hypothyroidism trial, the median IQ score of the children was 97 (95% confidence interval [CI], 94 to 99) in the levothyroxine group and 94 (95% CI, 92 to 96) in the placebo group (P=0.71). In the hypothyroxinemia trial, the median IQ score was 94 (95% CI, 91 to 95) in the levothyroxine group and 91 (95% CI, 89 to 93) in the placebo group (P=0.30). In each trial, IQ scores were missing for 4% of the children. There were no significant between-group differences in either trial in any other neurocognitive or pregnancy outcomes or in the incidence of adverse events, which was low in both groups. Conclusions Treatment for subclinical hypothyroidism or hypothyroxinemia beginning between 8 and 20 weeks of gestation did not result in significantly better cognitive outcomes in children through 5 years of age than no treatment for those conditions. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00388297 .).
PMID
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Screening and subsequent management for thyroid dysfunction pre-pregnancy and during pregnancy for improving maternal and infant health.

Authors

Mayor MeshTerms
Keywords
Journal Title the new england journal of medicine
Publication Year Start




PMID- 28249134
OWN - NLM
STAT- In-Process
DA  - 20170301
LR  - 20170301
IS  - 1533-4406 (Electronic)
IS  - 0028-4793 (Linking)
VI  - 376
IP  - 9
DP  - 2017 Mar 02
TI  - Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy.
PG  - 815-825
LID - 10.1056/NEJMoa1606205 [doi]
AB  - Background Subclinical thyroid disease during pregnancy may be associated with
      adverse outcomes, including a lower-than-normal IQ in offspring. It is unknown
      whether levothyroxine treatment of women who are identified as having subclinical
      hypothyroidism or hypothyroxinemia during pregnancy improves cognitive function
      in their children. Methods We screened women with a singleton pregnancy before 20
      weeks of gestation for subclinical hypothyroidism, defined as a thyrotropin level
      of 4.00 mU or more per liter and a normal free thyroxine (T4) level (0.86 to 1.90
      ng per deciliter [11 to 24 pmol per liter]), and for hypothyroxinemia, defined as
      a normal thyrotropin level (0.08 to 3.99 mU per liter) and a low free T4 level
      (&lt;0.86 ng per deciliter). In separate trials for the two conditions, women were
      randomly assigned to receive levothyroxine or placebo. Thyroid function was
      assessed monthly, and the levothyroxine dose was adjusted to attain a normal
      thyrotropin or free T4 level (depending on the trial), with sham adjustments for 
      placebo. Children underwent annual developmental and behavioral testing for 5
      years. The primary outcome was the IQ score at 5 years of age (or at 3 years of
      age if the 5-year examination was missing) or death at an age of less than 3
      years. Results A total of 677 women with subclinical hypothyroidism underwent
      randomization at a mean of 16.7 weeks of gestation, and 526 with hypothyroxinemia
      at a mean of 17.8 weeks of gestation. In the subclinical hypothyroidism trial,
      the median IQ score of the children was 97 (95% confidence interval [CI], 94 to
      99) in the levothyroxine group and 94 (95% CI, 92 to 96) in the placebo group
      (P=0.71). In the hypothyroxinemia trial, the median IQ score was 94 (95% CI, 91
      to 95) in the levothyroxine group and 91 (95% CI, 89 to 93) in the placebo group 
      (P=0.30). In each trial, IQ scores were missing for 4% of the children. There
      were no significant between-group differences in either trial in any other
      neurocognitive or pregnancy outcomes or in the incidence of adverse events, which
      was low in both groups. Conclusions Treatment for subclinical hypothyroidism or
      hypothyroxinemia beginning between 8 and 20 weeks of gestation did not result in 
      significantly better cognitive outcomes in children through 5 years of age than
      no treatment for those conditions. (Funded by the Eunice Kennedy Shriver National
      Institute of Child Health and Human Development and the National Institute of
      Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00388297 .).
FAU - Casey, Brian M
AU  - Casey BM
AD  - From the University of Texas Southwestern Medical Center, Dallas (B.M.C.), the
      University of Texas Medical Branch, Galveston (G.S.), and the University of Texas
      Health Science Center at Houston, McGovern Medical School-Children's Memorial
      Hermann Hospital, Houston (B.S.) - all in Texas; George Washington University
      Biostatistics Center, Washington, DC (E.A.T.); Northwestern University, Chicago
      (A.M.P.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.);
      Wayne State University, Detroit (Y.S.); the National Institute of Neurological
      Disorders and Stroke (D.G.H.) and the Eunice Kennedy Shriver National Institute
      of Child Health and Human Development (U.M.R.), Bethesda, MD; Columbia
      University, New York (R.J.W.); the University of North Carolina at Chapel Hill,
      Chapel Hill (J.M.T.); the University of Alabama at Birmingham, Birmingham
      (A.T.N.T.); Brown University, Providence, RI (D.J.R.); Ohio State University,
      Columbus (J.D.I.), and MetroHealth Medical Center-Case Western Reserve
      University, Cleveland (B.M.M.) - both in Ohio; Oregon Health and Science
      University, Portland (J.T.); University of Pittsburgh, Pittsburgh (S.N.C.); and
      the Medical University of South Carolina, Charleston (J.P.V.).
FAU - Thom, Elizabeth A
AU  - Thom EA
AD  - From the University of Texas Southwestern Medical Center, Dallas (B.M.C.), the
      University of Texas Medical Branch, Galveston (G.S.), and the University of Texas
      Health Science Center at Houston, McGovern Medical School-Children's Memorial
      Hermann Hospital, Houston (B.S.) - all in Texas; George Washington University
      Biostatistics Center, Washington, DC (E.A.T.); Northwestern University, Chicago
      (A.M.P.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.);
      Wayne State University, Detroit (Y.S.); the National Institute of Neurological
      Disorders and Stroke (D.G.H.) and the Eunice Kennedy Shriver National Institute
      of Child Health and Human Development (U.M.R.), Bethesda, MD; Columbia
      University, New York (R.J.W.); the University of North Carolina at Chapel Hill,
      Chapel Hill (J.M.T.); the University of Alabama at Birmingham, Birmingham
      (A.T.N.T.); Brown University, Providence, RI (D.J.R.); Ohio State University,
      Columbus (J.D.I.), and MetroHealth Medical Center-Case Western Reserve
      University, Cleveland (B.M.M.) - both in Ohio; Oregon Health and Science
      University, Portland (J.T.); University of Pittsburgh, Pittsburgh (S.N.C.); and
      the Medical University of South Carolina, Charleston (J.P.V.).
FAU - Peaceman, Alan M
AU  - Peaceman AM
AD  - From the University of Texas Southwestern Medical Center, Dallas (B.M.C.), the
      University of Texas Medical Branch, Galveston (G.S.), and the University of Texas
      Health Science Center at Houston, McGovern Medical School-Children's Memorial
      Hermann Hospital, Houston (B.S.) - all in Texas; George Washington University
      Biostatistics Center, Washington, DC (E.A.T.); Northwestern University, Chicago
      (A.M.P.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.);
      Wayne State University, Detroit (Y.S.); the National Institute of Neurological
      Disorders and Stroke (D.G.H.) and the Eunice Kennedy Shriver National Institute
      of Child Health and Human Development (U.M.R.), Bethesda, MD; Columbia
      University, New York (R.J.W.); the University of North Carolina at Chapel Hill,
      Chapel Hill (J.M.T.); the University of Alabama at Birmingham, Birmingham
      (A.T.N.T.); Brown University, Providence, RI (D.J.R.); Ohio State University,
      Columbus (J.D.I.), and MetroHealth Medical Center-Case Western Reserve
      University, Cleveland (B.M.M.) - both in Ohio; Oregon Health and Science
      University, Portland (J.T.); University of Pittsburgh, Pittsburgh (S.N.C.); and
      the Medical University of South Carolina, Charleston (J.P.V.).
FAU - Varner, Michael W
AU  - Varner MW
AD  - From the University of Texas Southwestern Medical Center, Dallas (B.M.C.), the
      University of Texas Medical Branch, Galveston (G.S.), and the University of Texas
      Health Science Center at Houston, McGovern Medical School-Children's Memorial
      Hermann Hospital, Houston (B.S.) - all in Texas; George Washington University
      Biostatistics Center, Washington, DC (E.A.T.); Northwestern University, Chicago
      (A.M.P.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.);
      Wayne State University, Detroit (Y.S.); the National Institute of Neurological
      Disorders and Stroke (D.G.H.) and the Eunice Kennedy Shriver National Institute
      of Child Health and Human Development (U.M.R.), Bethesda, MD; Columbia
      University, New York (R.J.W.); the University of North Carolina at Chapel Hill,
      Chapel Hill (J.M.T.); the University of Alabama at Birmingham, Birmingham
      (A.T.N.T.); Brown University, Providence, RI (D.J.R.); Ohio State University,
      Columbus (J.D.I.), and MetroHealth Medical Center-Case Western Reserve
      University, Cleveland (B.M.M.) - both in Ohio; Oregon Health and Science
      University, Portland (J.T.); University of Pittsburgh, Pittsburgh (S.N.C.); and
      the Medical University of South Carolina, Charleston (J.P.V.).
FAU - Sorokin, Yoram
AU  - Sorokin Y
AD  - From the University of Texas Southwestern Medical Center, Dallas (B.M.C.), the
      University of Texas Medical Branch, Galveston (G.S.), and the University of Texas
      Health Science Center at Houston, McGovern Medical School-Children's Memorial
      Hermann Hospital, Houston (B.S.) - all in Texas; George Washington University
      Biostatistics Center, Washington, DC (E.A.T.); Northwestern University, Chicago
      (A.M.P.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.);
      Wayne State University, Detroit (Y.S.); the National Institute of Neurological
      Disorders and Stroke (D.G.H.) and the Eunice Kennedy Shriver National Institute
      of Child Health and Human Development (U.M.R.), Bethesda, MD; Columbia
      University, New York (R.J.W.); the University of North Carolina at Chapel Hill,
      Chapel Hill (J.M.T.); the University of Alabama at Birmingham, Birmingham
      (A.T.N.T.); Brown University, Providence, RI (D.J.R.); Ohio State University,
      Columbus (J.D.I.), and MetroHealth Medical Center-Case Western Reserve
      University, Cleveland (B.M.M.) - both in Ohio; Oregon Health and Science
      University, Portland (J.T.); University of Pittsburgh, Pittsburgh (S.N.C.); and
      the Medical University of South Carolina, Charleston (J.P.V.).
FAU - Hirtz, Deborah G
AU  - Hirtz DG
AD  - From the University of Texas Southwestern Medical Center, Dallas (B.M.C.), the
      University of Texas Medical Branch, Galveston (G.S.), and the University of Texas
      Health Science Center at Houston, McGovern Medical School-Children's Memorial
      Hermann Hospital, Houston (B.S.) - all in Texas; George Washington University
      Biostatistics Center, Washington, DC (E.A.T.); Northwestern University, Chicago
      (A.M.P.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.);
      Wayne State University, Detroit (Y.S.); the National Institute of Neurological
      Disorders and Stroke (D.G.H.) and the Eunice Kennedy Shriver National Institute
      of Child Health and Human Development (U.M.R.), Bethesda, MD; Columbia
      University, New York (R.J.W.); the University of North Carolina at Chapel Hill,
      Chapel Hill (J.M.T.); the University of Alabama at Birmingham, Birmingham
      (A.T.N.T.); Brown University, Providence, RI (D.J.R.); Ohio State University,
      Columbus (J.D.I.), and MetroHealth Medical Center-Case Western Reserve
      University, Cleveland (B.M.M.) - both in Ohio; Oregon Health and Science
      University, Portland (J.T.); University of Pittsburgh, Pittsburgh (S.N.C.); and
      the Medical University of South Carolina, Charleston (J.P.V.).
FAU - Reddy, Uma M
AU  - Reddy UM
AD  - From the University of Texas Southwestern Medical Center, Dallas (B.M.C.), the
      University of Texas Medical Branch, Galveston (G.S.), and the University of Texas
      Health Science Center at Houston, McGovern Medical School-Children's Memorial
      Hermann Hospital, Houston (B.S.) - all in Texas; George Washington University
      Biostatistics Center, Washington, DC (E.A.T.); Northwestern University, Chicago
      (A.M.P.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.);
      Wayne State University, Detroit (Y.S.); the National Institute of Neurological
      Disorders and Stroke (D.G.H.) and the Eunice Kennedy Shriver National Institute
      of Child Health and Human Development (U.M.R.), Bethesda, MD; Columbia
      University, New York (R.J.W.); the University of North Carolina at Chapel Hill,
      Chapel Hill (J.M.T.); the University of Alabama at Birmingham, Birmingham
      (A.T.N.T.); Brown University, Providence, RI (D.J.R.); Ohio State University,
      Columbus (J.D.I.), and MetroHealth Medical Center-Case Western Reserve
      University, Cleveland (B.M.M.) - both in Ohio; Oregon Health and Science
      University, Portland (J.T.); University of Pittsburgh, Pittsburgh (S.N.C.); and
      the Medical University of South Carolina, Charleston (J.P.V.).
FAU - Wapner, Ronald J
AU  - Wapner RJ
AD  - From the University of Texas Southwestern Medical Center, Dallas (B.M.C.), the
      University of Texas Medical Branch, Galveston (G.S.), and the University of Texas
      Health Science Center at Houston, McGovern Medical School-Children's Memorial
      Hermann Hospital, Houston (B.S.) - all in Texas; George Washington University
      Biostatistics Center, Washington, DC (E.A.T.); Northwestern University, Chicago
      (A.M.P.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.);
      Wayne State University, Detroit (Y.S.); the National Institute of Neurological
      Disorders and Stroke (D.G.H.) and the Eunice Kennedy Shriver National Institute
      of Child Health and Human Development (U.M.R.), Bethesda, MD; Columbia
      University, New York (R.J.W.); the University of North Carolina at Chapel Hill,
      Chapel Hill (J.M.T.); the University of Alabama at Birmingham, Birmingham
      (A.T.N.T.); Brown University, Providence, RI (D.J.R.); Ohio State University,
      Columbus (J.D.I.), and MetroHealth Medical Center-Case Western Reserve
      University, Cleveland (B.M.M.) - both in Ohio; Oregon Health and Science
      University, Portland (J.T.); University of Pittsburgh, Pittsburgh (S.N.C.); and
      the Medical University of South Carolina, Charleston (J.P.V.).
FAU - Thorp, John M Jr
AU  - Thorp JM Jr
AD  - From the University of Texas Southwestern Medical Center, Dallas (B.M.C.), the
      University of Texas Medical Branch, Galveston (G.S.), and the University of Texas
      Health Science Center at Houston, McGovern Medical School-Children's Memorial
      Hermann Hospital, Houston (B.S.) - all in Texas; George Washington University
      Biostatistics Center, Washington, DC (E.A.T.); Northwestern University, Chicago
      (A.M.P.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.);
      Wayne State University, Detroit (Y.S.); the National Institute of Neurological
      Disorders and Stroke (D.G.H.) and the Eunice Kennedy Shriver National Institute
      of Child Health and Human Development (U.M.R.), Bethesda, MD; Columbia
      University, New York (R.J.W.); the University of North Carolina at Chapel Hill,
      Chapel Hill (J.M.T.); the University of Alabama at Birmingham, Birmingham
      (A.T.N.T.); Brown University, Providence, RI (D.J.R.); Ohio State University,
      Columbus (J.D.I.), and MetroHealth Medical Center-Case Western Reserve
      University, Cleveland (B.M.M.) - both in Ohio; Oregon Health and Science
      University, Portland (J.T.); University of Pittsburgh, Pittsburgh (S.N.C.); and
      the Medical University of South Carolina, Charleston (J.P.V.).
FAU - Saade, George
AU  - Saade G
AD  - From the University of Texas Southwestern Medical Center, Dallas (B.M.C.), the
      University of Texas Medical Branch, Galveston (G.S.), and the University of Texas
      Health Science Center at Houston, McGovern Medical School-Children's Memorial
      Hermann Hospital, Houston (B.S.) - all in Texas; George Washington University
      Biostatistics Center, Washington, DC (E.A.T.); Northwestern University, Chicago
      (A.M.P.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.);
      Wayne State University, Detroit (Y.S.); the National Institute of Neurological
      Disorders and Stroke (D.G.H.) and the Eunice Kennedy Shriver National Institute
      of Child Health and Human Development (U.M.R.), Bethesda, MD; Columbia
      University, New York (R.J.W.); the University of North Carolina at Chapel Hill,
      Chapel Hill (J.M.T.); the University of Alabama at Birmingham, Birmingham
      (A.T.N.T.); Brown University, Providence, RI (D.J.R.); Ohio State University,
      Columbus (J.D.I.), and MetroHealth Medical Center-Case Western Reserve
      University, Cleveland (B.M.M.) - both in Ohio; Oregon Health and Science
      University, Portland (J.T.); University of Pittsburgh, Pittsburgh (S.N.C.); and
      the Medical University of South Carolina, Charleston (J.P.V.).
FAU - Tita, Alan T N
AU  - Tita AT
AD  - From the University of Texas Southwestern Medical Center, Dallas (B.M.C.), the
      University of Texas Medical Branch, Galveston (G.S.), and the University of Texas
      Health Science Center at Houston, McGovern Medical School-Children's Memorial
      Hermann Hospital, Houston (B.S.) - all in Texas; George Washington University
      Biostatistics Center, Washington, DC (E.A.T.); Northwestern University, Chicago
      (A.M.P.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.);
      Wayne State University, Detroit (Y.S.); the National Institute of Neurological
      Disorders and Stroke (D.G.H.) and the Eunice Kennedy Shriver National Institute
      of Child Health and Human Development (U.M.R.), Bethesda, MD; Columbia
      University, New York (R.J.W.); the University of North Carolina at Chapel Hill,
      Chapel Hill (J.M.T.); the University of Alabama at Birmingham, Birmingham
      (A.T.N.T.); Brown University, Providence, RI (D.J.R.); Ohio State University,
      Columbus (J.D.I.), and MetroHealth Medical Center-Case Western Reserve
      University, Cleveland (B.M.M.) - both in Ohio; Oregon Health and Science
      University, Portland (J.T.); University of Pittsburgh, Pittsburgh (S.N.C.); and
      the Medical University of South Carolina, Charleston (J.P.V.).
FAU - Rouse, Dwight J
AU  - Rouse DJ
AD  - From the University of Texas Southwestern Medical Center, Dallas (B.M.C.), the
      University of Texas Medical Branch, Galveston (G.S.), and the University of Texas
      Health Science Center at Houston, McGovern Medical School-Children's Memorial
      Hermann Hospital, Houston (B.S.) - all in Texas; George Washington University
      Biostatistics Center, Washington, DC (E.A.T.); Northwestern University, Chicago
      (A.M.P.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.);
      Wayne State University, Detroit (Y.S.); the National Institute of Neurological
      Disorders and Stroke (D.G.H.) and the Eunice Kennedy Shriver National Institute
      of Child Health and Human Development (U.M.R.), Bethesda, MD; Columbia
      University, New York (R.J.W.); the University of North Carolina at Chapel Hill,
      Chapel Hill (J.M.T.); the University of Alabama at Birmingham, Birmingham
      (A.T.N.T.); Brown University, Providence, RI (D.J.R.); Ohio State University,
      Columbus (J.D.I.), and MetroHealth Medical Center-Case Western Reserve
      University, Cleveland (B.M.M.) - both in Ohio; Oregon Health and Science
      University, Portland (J.T.); University of Pittsburgh, Pittsburgh (S.N.C.); and
      the Medical University of South Carolina, Charleston (J.P.V.).
FAU - Sibai, Baha
AU  - Sibai B
AD  - From the University of Texas Southwestern Medical Center, Dallas (B.M.C.), the
      University of Texas Medical Branch, Galveston (G.S.), and the University of Texas
      Health Science Center at Houston, McGovern Medical School-Children's Memorial
      Hermann Hospital, Houston (B.S.) - all in Texas; George Washington University
      Biostatistics Center, Washington, DC (E.A.T.); Northwestern University, Chicago
      (A.M.P.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.);
      Wayne State University, Detroit (Y.S.); the National Institute of Neurological
      Disorders and Stroke (D.G.H.) and the Eunice Kennedy Shriver National Institute
      of Child Health and Human Development (U.M.R.), Bethesda, MD; Columbia
      University, New York (R.J.W.); the University of North Carolina at Chapel Hill,
      Chapel Hill (J.M.T.); the University of Alabama at Birmingham, Birmingham
      (A.T.N.T.); Brown University, Providence, RI (D.J.R.); Ohio State University,
      Columbus (J.D.I.), and MetroHealth Medical Center-Case Western Reserve
      University, Cleveland (B.M.M.) - both in Ohio; Oregon Health and Science
      University, Portland (J.T.); University of Pittsburgh, Pittsburgh (S.N.C.); and
      the Medical University of South Carolina, Charleston (J.P.V.).
FAU - Iams, Jay D
AU  - Iams JD
AD  - From the University of Texas Southwestern Medical Center, Dallas (B.M.C.), the
      University of Texas Medical Branch, Galveston (G.S.), and the University of Texas
      Health Science Center at Houston, McGovern Medical School-Children's Memorial
      Hermann Hospital, Houston (B.S.) - all in Texas; George Washington University
      Biostatistics Center, Washington, DC (E.A.T.); Northwestern University, Chicago
      (A.M.P.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.);
      Wayne State University, Detroit (Y.S.); the National Institute of Neurological
      Disorders and Stroke (D.G.H.) and the Eunice Kennedy Shriver National Institute
      of Child Health and Human Development (U.M.R.), Bethesda, MD; Columbia
      University, New York (R.J.W.); the University of North Carolina at Chapel Hill,
      Chapel Hill (J.M.T.); the University of Alabama at Birmingham, Birmingham
      (A.T.N.T.); Brown University, Providence, RI (D.J.R.); Ohio State University,
      Columbus (J.D.I.), and MetroHealth Medical Center-Case Western Reserve
      University, Cleveland (B.M.M.) - both in Ohio; Oregon Health and Science
      University, Portland (J.T.); University of Pittsburgh, Pittsburgh (S.N.C.); and
      the Medical University of South Carolina, Charleston (J.P.V.).
FAU - Mercer, Brian M
AU  - Mercer BM
AD  - From the University of Texas Southwestern Medical Center, Dallas (B.M.C.), the
      University of Texas Medical Branch, Galveston (G.S.), and the University of Texas
      Health Science Center at Houston, McGovern Medical School-Children's Memorial
      Hermann Hospital, Houston (B.S.) - all in Texas; George Washington University
      Biostatistics Center, Washington, DC (E.A.T.); Northwestern University, Chicago
      (A.M.P.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.);
      Wayne State University, Detroit (Y.S.); the National Institute of Neurological
      Disorders and Stroke (D.G.H.) and the Eunice Kennedy Shriver National Institute
      of Child Health and Human Development (U.M.R.), Bethesda, MD; Columbia
      University, New York (R.J.W.); the University of North Carolina at Chapel Hill,
      Chapel Hill (J.M.T.); the University of Alabama at Birmingham, Birmingham
      (A.T.N.T.); Brown University, Providence, RI (D.J.R.); Ohio State University,
      Columbus (J.D.I.), and MetroHealth Medical Center-Case Western Reserve
      University, Cleveland (B.M.M.) - both in Ohio; Oregon Health and Science
      University, Portland (J.T.); University of Pittsburgh, Pittsburgh (S.N.C.); and
      the Medical University of South Carolina, Charleston (J.P.V.).
FAU - Tolosa, Jorge
AU  - Tolosa J
AD  - From the University of Texas Southwestern Medical Center, Dallas (B.M.C.), the
      University of Texas Medical Branch, Galveston (G.S.), and the University of Texas
      Health Science Center at Houston, McGovern Medical School-Children's Memorial
      Hermann Hospital, Houston (B.S.) - all in Texas; George Washington University
      Biostatistics Center, Washington, DC (E.A.T.); Northwestern University, Chicago
      (A.M.P.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.);
      Wayne State University, Detroit (Y.S.); the National Institute of Neurological
      Disorders and Stroke (D.G.H.) and the Eunice Kennedy Shriver National Institute
      of Child Health and Human Development (U.M.R.), Bethesda, MD; Columbia
      University, New York (R.J.W.); the University of North Carolina at Chapel Hill,
      Chapel Hill (J.M.T.); the University of Alabama at Birmingham, Birmingham
      (A.T.N.T.); Brown University, Providence, RI (D.J.R.); Ohio State University,
      Columbus (J.D.I.), and MetroHealth Medical Center-Case Western Reserve
      University, Cleveland (B.M.M.) - both in Ohio; Oregon Health and Science
      University, Portland (J.T.); University of Pittsburgh, Pittsburgh (S.N.C.); and
      the Medical University of South Carolina, Charleston (J.P.V.).
FAU - Caritis, Steve N
AU  - Caritis SN
AD  - From the University of Texas Southwestern Medical Center, Dallas (B.M.C.), the
      University of Texas Medical Branch, Galveston (G.S.), and the University of Texas
      Health Science Center at Houston, McGovern Medical School-Children's Memorial
      Hermann Hospital, Houston (B.S.) - all in Texas; George Washington University
      Biostatistics Center, Washington, DC (E.A.T.); Northwestern University, Chicago
      (A.M.P.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.);
      Wayne State University, Detroit (Y.S.); the National Institute of Neurological
      Disorders and Stroke (D.G.H.) and the Eunice Kennedy Shriver National Institute
      of Child Health and Human Development (U.M.R.), Bethesda, MD; Columbia
      University, New York (R.J.W.); the University of North Carolina at Chapel Hill,
      Chapel Hill (J.M.T.); the University of Alabama at Birmingham, Birmingham
      (A.T.N.T.); Brown University, Providence, RI (D.J.R.); Ohio State University,
      Columbus (J.D.I.), and MetroHealth Medical Center-Case Western Reserve
      University, Cleveland (B.M.M.) - both in Ohio; Oregon Health and Science
      University, Portland (J.T.); University of Pittsburgh, Pittsburgh (S.N.C.); and
      the Medical University of South Carolina, Charleston (J.P.V.).
FAU - VanDorsten, J Peter
AU  - VanDorsten JP
AD  - From the University of Texas Southwestern Medical Center, Dallas (B.M.C.), the
      University of Texas Medical Branch, Galveston (G.S.), and the University of Texas
      Health Science Center at Houston, McGovern Medical School-Children's Memorial
      Hermann Hospital, Houston (B.S.) - all in Texas; George Washington University
      Biostatistics Center, Washington, DC (E.A.T.); Northwestern University, Chicago
      (A.M.P.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.);
      Wayne State University, Detroit (Y.S.); the National Institute of Neurological
      Disorders and Stroke (D.G.H.) and the Eunice Kennedy Shriver National Institute
      of Child Health and Human Development (U.M.R.), Bethesda, MD; Columbia
      University, New York (R.J.W.); the University of North Carolina at Chapel Hill,
      Chapel Hill (J.M.T.); the University of Alabama at Birmingham, Birmingham
      (A.T.N.T.); Brown University, Providence, RI (D.J.R.); Ohio State University,
      Columbus (J.D.I.), and MetroHealth Medical Center-Case Western Reserve
      University, Cleveland (B.M.M.) - both in Ohio; Oregon Health and Science
      University, Portland (J.T.); University of Pittsburgh, Pittsburgh (S.N.C.); and
      the Medical University of South Carolina, Charleston (J.P.V.).
CN  - Eunice Kennedy Shriver National Institute of Child Health and Human Development
      Maternal-Fetal Medicine Units Network
LA  - eng
SI  - ClinicalTrials.gov/NCT00388297
GR  - U10 HD034116/HD/NICHD NIH HHS/United States
GR  - U10 HD040512/HD/NICHD NIH HHS/United States
GR  - U10 HD027917/HD/NICHD NIH HHS/United States
GR  - U10 HD034208/HD/NICHD NIH HHS/United States
GR  - U10 HD040485/HD/NICHD NIH HHS/United States
GR  - U10 HD040560/HD/NICHD NIH HHS/United States
GR  - U10 HD053097/HD/NICHD NIH HHS/United States
GR  - U10 HD027869/HD/NICHD NIH HHS/United States
GR  - U10 HD040500/HD/NICHD NIH HHS/United States
GR  - U10 HD040545/HD/NICHD NIH HHS/United States
GR  - U10 HD027915/HD/NICHD NIH HHS/United States
GR  - U10 HD040544/HD/NICHD NIH HHS/United States
GR  - U10 HD053118/HD/NICHD NIH HHS/United States
GR  - U10 HD021410/HD/NICHD NIH HHS/United States
GR  - U01 HD036801/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
CIN - N Engl J Med. 2017 Mar 2;376(9):876-877. PMID: 28249140
EDAT- 2017/03/02 06:00
MHDA- 2017/03/02 06:00
CRDT- 2017/03/02 06:00
AID - 10.1056/NEJMoa1606205 [doi]
PST - ppublish
SO  - N Engl J Med. 2017 Mar 2;376(9):815-825. doi: 10.1056/NEJMoa1606205.

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