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<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="lEi5HIFDObN8kkCWADcnivPOtHrFPCspCr2aky8ZoMACeLIMdWPpMDls1L9RId0J">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="lEi5HIFDObN8kkCWADcnivPOtHrFPCspCr2aky8ZoMACeLIMdWPpMDls1L9RId0J">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="lEi5HIFDObN8kkCWADcnivPOtHrFPCspCr2aky8ZoMACeLIMdWPpMDls1L9RId0J">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="lEi5HIFDObN8kkCWADcnivPOtHrFPCspCr2aky8ZoMACeLIMdWPpMDls1L9RId0J">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="lEi5HIFDObN8kkCWADcnivPOtHrFPCspCr2aky8ZoMACeLIMdWPpMDls1L9RId0J">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="33651557">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
book
dialog-focus"
href="https://www.ncbi.nlm.nih.gov/books/NBK567999"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3057&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=33651557&amp;db=pubmed"
title="See full text options at NCBI Bookshelf"
data-ga-category="full_text"
data-ga-action="NCBI Bookshelf"
data-ga-label="33651557"
><img class="book-icon" src="https://cdn.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-dia3ed.png" alt="book cover photo"><div class="book-icon-label"><div class="book-icon-label-subtitle">CHAPTER 5</div><div class="book-icon-label-title">Diabetes in America</div></div><span class="text">
NCBI Bookshelf
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/33651557/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/33651557/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="33651557" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F33651557%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="lEi5HIFDObN8kkCWADcnivPOtHrFPCspCr2aky8ZoMACeLIMdWPpMDls1L9RId0J"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="collections_button"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
Choose a collection:
</label><select id="collections-action-dialog-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="collections_button"
data-ga-action="select_collection"
data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="add">
Add
</button><button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="cancel">
Cancel
</button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger"
title="Open dialog with more actions to take"
ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format"
data-default-format-value="abstract"
data-current-format-value="abstract" role="region"><button
class="trigger usa-button"
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Preexisting Diabetes and Pregnancy
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<div class="citation">In: Diabetes in America. 3rd edition. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases (US); 2018 Aug. CHAPTER 5.</div>
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<li data-affiliation-id="full-view-affiliation-1"
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><sup class="key">1</sup> Dr. John L. Kitzmiller retired in 2015 as Consultant in Maternal-Fetal Medicine and Director of the Diabetes and Pregnancy Program at Santa Clara County Medical and Health Centers, San Jose, CA, and previously as Professor of Obstetrics at UCSF, San Francisco, CA</li>
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><sup class="key">2</sup> Dr. Assiamira Ferrara is Associate Director of Womens and Childrens Health, Division of Research, Kaiser Permanente Northern California, Oakland, CA</li>
<li data-affiliation-id="full-view-affiliation-3"
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><sup class="key">3</sup> Ms. Tiffany Peng is Senior Data Consultant, Division of Research, Kaiser Permanente Northern California, Oakland, CA</li>
<li data-affiliation-id="full-view-affiliation-4"
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><sup class="key">4</sup> Dr. Michelle A. Cissell is a science writer and editor, Chicago, IL</li>
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><sup class="key">5</sup> Dr. Catherine Kim is Associate Professor of Medicine, Obstetrics &amp; Gynecology, and Epidemiology at the University of Michigan, Ann Arbor, MI</li>
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<li data-affiliation-id="full-view-book-affiliation-1"
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><sup class="key">1</sup> Senior Advisor and Director for Diabetes Epidemiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD</li>
<li data-affiliation-id="full-view-book-affiliation-2"
id="full-view-book-affiliation-2"
><sup class="key">2</sup> Senior Research Analyst, Social &amp; Scientific Systems, Inc., Silver Spring, MD</li>
<li data-affiliation-id="full-view-book-affiliation-3"
id="full-view-book-affiliation-3"
><sup class="key">3</sup> Science Writer/Editor, Chicago, IL</li>
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id="full-view-book-affiliation-4"
><sup class="key">4</sup> Epidemiologist, Division of Health and Nutrition Examination Surveys, National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, MD</li>
<li data-affiliation-id="full-view-book-affiliation-5"
id="full-view-book-affiliation-5"
><sup class="key">5</sup> Professor of Medicine, Harvard Medical School, and Physician, Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA</li>
<li data-affiliation-id="full-view-book-affiliation-6"
id="full-view-book-affiliation-6"
><sup class="key">6</sup> Chief, Epidemiology and Statistics Branch, Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA</li>
<li data-affiliation-id="full-view-book-affiliation-7"
id="full-view-book-affiliation-7"
><sup class="key">7</sup> Chief, Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ</li>
<li data-affiliation-id="full-view-book-affiliation-8"
id="full-view-book-affiliation-8"
><sup class="key">8</sup> Distinguished Professor, Division of Epidemiology, Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA</li>
<li data-affiliation-id="full-view-book-affiliation-9"
id="full-view-book-affiliation-9"
><sup class="key">9</sup> Professor of Pediatrics, Division of Endocrinology and Diabetes, Childrens Hospital of Pittsburgh of UPMC, Pittsburgh, PA</li>
<li data-affiliation-id="full-view-book-affiliation-10"
id="full-view-book-affiliation-10"
><sup class="key">10</sup> Distinguished Service Professor of Medicine and Epidemiology, Johns Hopkins University, Baltimore, MD</li>
<li data-affiliation-id="full-view-book-affiliation-11"
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><sup class="key">11</sup> Professor, University of Washington, and Staff Physician, Veterans Affairs Puget Sound, Seattle, WA</li>
<li data-affiliation-id="full-view-book-affiliation-12"
id="full-view-book-affiliation-12"
><sup class="key">12</sup> Professor, Departments of Internal Medicine and Epidemiology, University of Michigan, Ann Arbor, MI</li>
<li data-affiliation-id="full-view-book-affiliation-13"
id="full-view-book-affiliation-13"
><sup class="key">13</sup> Professor of Medicine, Department of Medicine, Division of Endocrinology and Metabolism, Georgetown University Hospital, and Senior Scientist, MedStar Health Research Institute, Hyattsville, MD</li>
<li data-affiliation-id="full-view-book-affiliation-14"
id="full-view-book-affiliation-14"
><sup class="key">14</sup> Director, Emory Global Diabetes Research Center, Ruth and O.C. Hubert Professor of Global Health and Epidemiology, Rollins School of Public Health, and Professor of Medicine, School of Medicine, Emory University, Atlanta, GA</li>
<li data-affiliation-id="full-view-book-affiliation-15"
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><sup class="key">15</sup> Professor of Pediatrics and Medicine, Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO</li>
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Preexisting Diabetes and Pregnancy
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<div class="citation">In: Diabetes in America. 3rd edition. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases (US); 2018 Aug. CHAPTER 5.</div>
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><sup class="key">1</sup> Dr. John L. Kitzmiller retired in 2015 as Consultant in Maternal-Fetal Medicine and Director of the Diabetes and Pregnancy Program at Santa Clara County Medical and Health Centers, San Jose, CA, and previously as Professor of Obstetrics at UCSF, San Francisco, CA</li>
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<p>
The prevalence of diabetes in adolescents and women of reproductive age has increased since 1995. However, no prospective national population-based data from the United States are available regarding women with preexisting diabetes in pregnancy (pregestational)—that is, type 1 diabetes or type 2 diabetes identified before pregnancy. Knowledge of the true prevalence depends on inclusion of women with early pregnancy losses, which are not available in birth certificate or hospital discharge data. In this chapter, prevalence data are presented from selected populations, including women who have recently given birth to a live infant, women who have used diabetes medications during pregnancy, women who have delivered in hospitals, and women enrolled in specific health plans. These reports, as well as population-based reports from other countries, suggest that diabetes during pregnancy <i>has at least doubled</i> since 1995, with increases in pregnancies affected by type 1 and type 2 diabetes and across all age groups.
</p>
<p>
Surveys of diabetes in female youth show that the prevalence of type 1 diabetes is greater than type 2 diabetes, but by the time in life of pregnancy, the ratio has reversed in population-based analyses of births. The former crude prevalence of preexisting diabetes mellitus in pregnancy of approximately 0.3% has risen to 1.0%1.9% in major parts of North America, paralleling the diabetes prevalence in reproductive-age women, which was approximately 1.85%3.0% between 2002 and 2009.
</p>
<p>
Preconception care of diabetes has consistently been reported to reduce major congenital malformations and perinatal complications by over 60%, thus rendering such care cost-effective. Utilization of preconception care is suboptimal, in part because of the high frequency of unplanned pregnancy, as well as lack of access to care. No national or regional surveillance systems are in place to prospectively monitor utilization of preconception care of diabetes and outcomes in the United States. Even though the risks of unplanned pregnancy are greater in women with diabetes than in nondiabetic women, women with diabetes are less likely to receive contraception counseling than women without diabetes.
</p>
<p>
Large prospective studies of diabetic women from the preconception period forward are needed in order to obtain reliable data on the prevalence of preconception care of diabetes and the use of contraception, as well as the number of diabetic women becoming and remaining pregnant. This effort might also have the effect of <i>better linkage of general diabetes care to enhanced preconception management of diabetic women</i>.
</p>
<p>
Severe maternal complications of pregnancy may be rare in the United States, but diabetes increases the relative risks of maternal mortality, ischemic stroke, myocardial infarction, preeclampsia-eclampsia, and possibly sepsis and venous thromboembolism. Prevention of diabetic ketoacidosis and severe maternal hypoglycemia is crucial; their frequencies should be monitored as indicators of quality of care, including self-care by the patient. Population-based systems to monitor these important comorbidities are lacking in the United States.
</p>
<p>
Proliferative retinopathy can progress during pregnancy, but risk of vision loss can be reduced by comprehensive ophthalmologic screening and photocoagulation as necessary. Data from other countries suggest that pregnancy does not exacerbate mild nephropathy in the long term, although the presence of nephropathy can contribute to poorer birth outcomes and worsen prognosis over the long term. Hypertensive disorders affect &gt;10% of diabetic pregnancies, contributing to neonatal morbidity. Prospective data on treatment of hypertension during diabetic pregnancy are lacking.
</p>
<p>
First trimester glycosylated hemoglobin (A1c) levels &gt;7.0% are associated with poorer birth outcomes. The teratogenic effects of hyperglycemia may be compounded by obesity, smoking, alcohol use, and/or poor nutrition. Fetal complications include a higher frequency of major congenital malformations, the most common of which are cardiovascular. It is controversial whether the use of medications common among women with diabetes contributes to the malformation risk, although insulin, antihyperglycemic medications, and oral contraceptives do not appear to do so. Stillbirths occur more frequently among women with poorer glucose control, and degree of risk increases with degree of A1c elevation. The prevalences of major malformations and stillbirths in surveys depend on the inclusion of terminations of pregnancy or late fetal losses at 2023 weeks gestation, respectively.
</p>
<p>
Women with diabetes also have a 30%60% higher risk of infants affected by preterm delivery and macrosomia with concomitant birth trauma events, such as shoulder dystocia with vaginal delivery. In 2009, approximately 56.5% of births to women with pregestational diabetes mellitus were by cesarean section, and 16%27% of births resulted in birth weights &gt;4,000 g. Other adverse events among infants of mothers with diabetes include infant mortality and neonatal hypoxic-ischemic encephalopathy, although such events are infrequent. Infants of diabetic mothers can experience a higher frequency of respiratory distress, polycythemia, hypoglycemia, hypocalcemia, and hyperbilirubinemia compared to infants of mothers without diabetes. In rare cases, these complications also can contribute to neonatal encephalopathy.
</p>
<p>
The increasing frequency of type 1 and type 2 diabetes in young women and increasing maternal age at conception are likely to further increase the risk of adverse maternal, birth, and infant outcomes. Population-based data are needed to track conception, miscarriage, major malformations, and livebirth and stillbirth frequencies among women with diabetes. Such data would guide the optimal timing and tailoring of preconception interventions. Interventions are needed that quantify the optimal amount of surveillance during fetal development (balancing costs and benefits), along with interventions that examine long-term risk to mothers and offspring.
</p>
<p>
The subject matter in this chapter is necessarily broad, as it not only discusses prevalence of pregestational diabetes mellitus in pregnancy but also prevalence of diabetes in reproductive-age women; preconception care and contraception; complications in the mother, fetus, infant, and developing offspring; and methodologic issues related to assessment of outcomes in the mother, fetus, and infant. The beauty and the devil is in the details. The definitions and management of pregnancy-related conditions can vary considerably among studies and, in many cases, are controversial.
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<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one"><bold>DUALITY OF INTEREST</bold></p>
<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">Drs. Kitzmiller, Ferrara, Cissell, and Kim and Ms. Peng reported no conflicts of interest.</p>
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<div class="book-sections" id="book-sections">
<h2 class="title">
Sections
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<ul>
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<a href="https://www.ncbi.nlm.nih.gov/books/NBK567999/#ch5.sum" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
Summary
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<a href="https://www.ncbi.nlm.nih.gov/books/NBK567999/#ch5.s1" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
Introduction
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<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK567999/#ch5.s2" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
Considerations Before Pregnancy
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</li>
<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK567999/#ch5.s3" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
Prevalence of Preexisting Diabetes During Pregnancy
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</li>
<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK567999/#ch5.s4" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
Maternal Complications Before and During Pregnancy
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</li>
<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK567999/#ch5.s5" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
Fetal Complications Prior to Delivery
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</li>
<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK567999/#ch5.s6" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
Complications of Delivery
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<li>
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Neonatal Complications in Infants of Mothers With Preexisting Diabetes
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<li>
<a href="https://www.ncbi.nlm.nih.gov/books/NBK567999/#ch5.s8" target="_blank" rel="noopener" ref="linksrc=book_abstract_section_link">
Epidemiologic Studies of Methods of Management of Diabetes in Pregnancy
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<li>
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Health Risks in Children of Mothers With Diabetes Before and During Pregnancy
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List of Abbreviations
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References
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<p>Diabetic women viewing a preconception counselling DVD had significantly improved pregnancy planning indicators. Women with type 2 diabetes were difficult to reach.</p>
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<p>Searched for quantitative studies of preconception care education published from 2003 to June 2016; reviewed 12 studies. All studies showed a positive effect on pregnancy outcomes.</p>
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<p>Only 64% of 455 type 1 diabetic women who considered their pregnancy as planned received actual prepregnancy counselling. Of 747 diabetic women, 39% considered their pregnancy unplanned; they had higher A1c levels throughout pregnancy and their infants were more likely to be SGA and to be admitted to the NICU, with a longer stay in hospital.</p>
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<p>European panelists agreed on nine measures of pregnancy preparation, six neonatal outcomes, and two maternal outcomes to be used in future studies of preconception care of diabetic women.</p>
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Haghighat N, Hu M, Laurent O, Chung J, Nguyen P, Wu J: Comparison of birth certificates and hospital-based birth data on pregnancy complications in Los Angeles and Orange County, California. BMC Pregnancy Childbirth 16:93, 2016. Apr 27 [Epub] doi: 10.1186/s12884-016-0885-0
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href="https://doi.org/10.1186/s12884-016-0885-0"
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data-ga-action="10.1186/s12884-016-0885-0"
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DOI
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href="https://pmc.ncbi.nlm.nih.gov/articles/PMC4848813/"
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PMC
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PubMed
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<p>Diabetes was underreported in birth certificate data (1.97%) compared to a hospital system perinatal research database (5.56%). Underreporting was significantly higher among Hispanic women compared to non-Hispanic white women and among all women with public insurance.</p>
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Robledo CA, Yeung EH, Mendola P, Sundaram R, Boghossian NS, Bell EM, Druschel C: Examining the prevalence rates of preexisting maternal medical conditions and pregnancy complications by source: evidence to inform maternal and child research. Matern Child Health J 21:852862, 2017
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PMC
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<p>Ascertained diagnoses of preexisting diabetes and chronic hypertension according to birth certificates, maternal self-report 4 months postpartum, and a mandated New York statewide hospital reporting system for discharge codes.</p>
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<ol class="references-and-notes-list">
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Mayer-Davis EJ, Lawrence JM, Dabelea D, Divers J, Isom S, Dolan L, Imperatore G, Linder B, Marcovina S, Pettitt DJ, Pihoker C, Saydah S, Wagenknecht L; SEARCH for Diabetes in Youth Study: Incidence trends of type 1 and type 2 diabetes among youths, 20022012. N Engl J Med 376:14191429, 2017
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href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5592722/"
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PubMed
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<p>Ascertained cases of type 1 diabetes (age 019 years) and type 2 diabetes (age 1019 years) at five study centers in the United States for the period 20022012; denominators (4.9 million youths annually) obtained from the U.S. Census or health plan member counts; after adjustment for age, sex, and race or ethnic group, the relative annual increase in the incidence of type 1 diabetes was 1.8% (21.7 cases per 100,000 youths per year in 20112012) and 4.8% for type 2 diabetes (12.5 cases per 100,000 youths in 20112012).</p>
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Coton SJ, Nazareth I, Petersen I: A cohort study of trends in the prevalence of pregestational diabetes in pregnancy recorded in UK general practice between 1995 and 2012. BMJ Open 6:e009494, 2016. Jan 25 [Epub] doi: 10.1136/bmjopen-2015-009494
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<a
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href="https://doi.org/10.1136/bmjopen-2015-009494"
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DOI
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<p>Prevalence of type 1 diabetes in pregnancy increased from 0.16% in 1995 to 0.41% in 2015; prevalence of type 2 diabetes increased from 0.23% in 1995 to 1.06% in 2012.</p>
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value="1">
Fadl HE, Simmons D: Trends in diabetes in pregnancy in Sweden 19982012. BMJ Open Diabetes Res Care 4:e000221, 2016. Aug 11 [Epub] doi: 10.1136/bmjdrc-2016-000221
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<p>Using Swedish national medical birth registry data (84% to 76.5% Nordic origin), over the 15-year period, type 1 diabetes increased by 33.2% (prevalence 0.38% in 19982000 and 0.47% in 20102012; stable since 2004) and type 2 diabetes by 111% (prevalence 0.03% in 19982000 and 0.10% in 20102012; steady increase), adjusted for maternal BMI, ethnicity, and age in a logistic regression model.</p>
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</div>
<div class="refs-list">
<h4 class="refs-list-title">Maternal Complications</h4>
<ol id="top-references-list-4" class="references-list">
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<ol class="references-and-notes-list">
<li
value="1">
Persson M, Cnattingius S, Wikstrom AK, Johansson S: Maternal overweight and obesity and risk of preeclampsia in women with type 1 diabetes or type 2 diabetes. Diabetologia 59:20992105, 2016
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<a
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href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5016540/"
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data-ga-action="PMC5016540"
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PMC
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<p>Among 1,532,682 singleton births in Sweden in 19972012, 0.46% of mothers were registered as type 1 diabetes and 0.06% as type 2 diabetes. Preeclampsia was diagnosed in 15.6% of pregnant women with type 1 diabetes and 9.7% with type 2 diabetes compared to 2.8% of nondiabetic controls; preeclampsia was severe in 5.6% of women with type 1 diabetes, 3.2% with type 2 diabetes, and 0.9% of nondiabetic controls.</p>
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Morrison FJ, Movassaghian M, Seely EW, Curran A, Shubina M, Morton-Eggleston E, Zera CA, Ecker JL, Brown FM, Turchin A: Fetal outcomes after diabetic ketoacidosis during pregnancy. Diabetes Care 40:e77e79, 2017, Jul [Epub] doi: 10.2337/dc17-0186
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<a
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href="https://doi.org/10.2337/dc17-0186"
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DOI
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<a
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href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5481983/"
ref="linksrc=references_link&amp;ordinalpos=2"
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PMC
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PubMed
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<p>In a multicenter study in Boston, Massachusetts, between 1995 and 2015, there were 77 DKA events in 64 pregnancies; fetal demise occurred at the time of or within one week of the event in 9.4% and eventual preterm delivery in 46.3%.</p>
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</div>
<div class="refs-list">
<h4 class="refs-list-title">Birth Outcomes</h4>
<ol id="top-references-list-5" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
value="1">
Murphy HR, Bell R, Cartwright C, Curnow P, Maresh M, Morgan M, Sylvester C, Young B, Lewis-Barned N: Improved pregnancy outcomes in women with type 1 and type 2 diabetes but substantial clinic-to-clinic variations: a prospective nationwide study. Diabetologia 60:16681677, 2017
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<a
class="reference-link"
href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5552835/"
ref="linksrc=references_link&amp;ordinalpos=1"
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data-ga-action="PMC5552835"
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PMC
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<a
class="reference-link"
href="/28597075/"
ref="linksrc=references_link&amp;ordinalpos=2"
data-ga-category="reference"
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PubMed
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<p>Cohort included 3,036 pregnant women from 155 maternity clinics in England and Wales in 2015 (46% type 2 diabetes). Preterm delivery: 39.7% in type 1 diabetes and 21.7% in type 2 diabetes. LGA infants: 46.4% of type 1 diabetes and 23.9% of type 2 diabetes. Congenital anomaly: 4.6% in type 1 diabetes and 3.5% in type 2 diabetes. Stillbirth: 1.1% in type 1 diabetes and 1.05% in type 2 diabetes. Neonatal death: 0.8% in type 1 diabetes and 1.1% in type 2 diabetes.</p>
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value="1">
Allen AJ, Snowden JM, Lau B, Cheng Y, Caughey AB: Type-2 diabetes mellitus: does prenatal care affect outcomes? J Matern Fetal Neonatal Med 31:9397, 2017
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PubMed
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<p>Based on vital statistics data linked to birth certificates in California from 19972006, women with pregestational type 2 diabetes who presented for care at the time of delivery (no prenatal care) had an 11.3% risk of stillbirth compared to 0.9% in those who presented in the first trimester.</p>
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Strom-Roum EM, Tanbo TG, Eskild A: The associations of maternal body mass index with birthweight and placental weight. Does maternal diabetes matter? A population study of 106 191 pregnancies. Acta Obstet Gynecol Scand 95:11621170, 2016
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href="/27454190/"
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<p>Based on data in the Medical Birth Registry of Norway from 20092012, mean birthweight and placental weight were significantly higher in pregnancies of type 1 diabetic women compared to pregnancies without diabetes, but there was no influence of maternal BMI on birthweight or placental weight in type 1 diabetes (as there was in nondiabetic women or gestational diabetes).</p>
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Abell SK, Boyle JA, de Courten B, Knight M, Ranasinha S, Regan J, Soldatos G, Wallace EM, Zoungas S, Teede HJ: Contemporary type 1 diabetes pregnancy outcomes: impact of obesity and glycemic control. Med J Aust 205:162167, 2016
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<p>Analyzed all singleton births ≥20 weeks of women with type 1 diabetes in a specialist diabetes and maternity care network in the region of Victoria, Australia, for 20102013 compared to 27,075 control pregnancies. Significant adjusted odds ratios &gt;4.0 for diabetic risk were found for increased rates of preterm delivery, fetal macrosomia, shoulder dystocia, perinatal death, and neonatal hypoglycemia and jaundice.</p>
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<div class="refs-list">
<h4 class="refs-list-title">Congenital Malformations</h4>
<ol id="top-references-list-6" class="references-list">
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<li
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Persson M, Cnattingius S, Villamor E, Soderling J, Pasternak B, Stephansson O, Neovius M: Risk of major congenital malformations in relation to maternal overweight and obesity severity: cohort study of 1.2 million singletons. BMJ 357:j2563, 2017. Jun 14 [Epub] doi: 10.1136/bmj.j2563
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href="https://doi.org/10.1136/bmj.j2563"
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data-ga-action="10.1136/bmj.j2563"
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DOI
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<a
class="reference-link"
href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5470075/"
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data-ga-category="reference"
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PubMed
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<p>Analyzed liveborn singleton infants without chromosomal aberrations or syndromes born ≥22 weeks in Sweden from 2001 to 2014; 3.5% of offspring had any major congenital malformation (43,550 events); 46% were congenital heart defects. Overall, major malformations were more likely in boys than girls (adjusted OR 1.46, 95% CI 1.431.49), especially for genital, urinary tract, and limb malformations; congenital heart defects were reported in 1.67% of girls and 1.56% of boys. There was a limited stepwise association of risk with increasing maternal BMI (in both fetal sexes), with number of cigarettes smoked per day, but not with increasing maternal age. The major adjusted effects of increasing maternal BMI ≥30 kg/m<sup>2</sup> were seen for congenital heart defects, nervous system defects, orofacial clefts, digestive system defects in boys, and genital organs. Sensitivity analysis excluding 2,860 events associated with maternal pregestational diabetes mellitus (6.6% of total events) did not change the results.</p>
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<li
value="1">
Agha MM, Glazier RH, Moineddin R, Booth G: Congenital abnormalities in newborns of women with pregestational diabetes: a timetrend analysis, 1994 to 2009. Birth Defects Res A Clin Mol Teratol 106:831839, 2016
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href="/27511615/"
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data-ga-category="reference"
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<p>Surveyed all liveborns and their mothers in Ontario, Canada; the prevalence of births among diabetic mothers increased by almost 200% during the study period. In their children, the prevalence for all anomalies combined was 47% higher and for various cardiac and central nervous system anomalies up to a threefold to fivefold higher rate than in those born to nondiabetic mothers. The rate of birth defects in both groups declined after folate food fortification in 1999, but the excess risk associated with maternal pregestational diabetes mellitus remained.</p>
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value="1">
Feldkamp ML, Carey JC, Byrne JL, Krikov S, Botto LD: Etiology and clinical presentation of birth defects: population based study. BMJ 357:j2249, 2017. May 30 [Epub] doi: 10.1136/bmj.j2249
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href="https://doi.org/10.1136/bmj.j2249"
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DOI
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href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5448402/"
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<p>Reviewed 5,504 cases of birth defects among 270,878 births (prevalence 2.03%) in Utah in 20052009. Only 20.2% could have a definite cause assigned: chromosomal or genetic conditions in 19.1% of total cases, conjoined or acardiac twinning in 0.29%, and poorly controlled pregestational diabetes mellitus in 0.6%. In the latter group, 75% of cases had ≥2 major anomalies in the same fetus (vs. 15.7% in total nondiabetic group) with a 28% fetal loss rate (stillbirths and terminations of pregnancy) with multiple anomalies in maternal diabetes versus a 15.1% fetal loss rate with multiple major anomalies without maternal diabetes.</p>
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Oyen N, Diaz LJ, Leirgul E, Boyd HA, Priest J, Mathiesen ER, Quertermous T, Wohlfahrt J, Melbye M: Prepregnancy diabetes and offspring risk of congenital heart disease: a nationwide cohort study. Circulation 133:22432253, 2016
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<a
class="reference-link"
href="https://pmc.ncbi.nlm.nih.gov/articles/PMC4890838/"
ref="linksrc=references_link&amp;ordinalpos=1"
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data-ga-action="PMC4890838"
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PMC
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class="reference-link"
href="/27166384/"
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data-ga-category="reference"
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PubMed
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<p>In a Danish national cohort from 19782011, 0.36% of infants were exposed to maternal pregestational diabetes mellitus; the prevalence of congenital heart disease in them was 3.18% in comparison with a baseline rate of 0.80% (adjusted RR 4.00, 95% CI 3.514.53). The association was not modified by year of birth, maternal age at diabetes onset, or duration or type of diabetes. All specific congenital heart defect phenotypes were associated with maternal pregestational diabetes mellitus (RR range 2.7413.8).</p>
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Leirgul E, Brodwall K, Greve G, Vollset SE, Holmstrom H, Tell GS, Oyen N: Maternal diabetes, birth weight, and neonatal risk of congenital heart defects in Norway, 19942009. Obstet Gynecol 128:11161125, 2016
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PubMed
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<p>Of 914,427 live births, stillbirths, and terminated pregnancies, 0.61% were complicated by maternal pregestational diabetes mellitus. In the latter group, the prevalence of offspring with cardiac defects was 3.44% versus 1.14% without diabetes (adjusted RR 2.92, 95% CI 2.543.36). The associated risk did not change during the study period. Within the pregestational diabetes mellitus group, the prevalence of congenital heart defects in very macrosomic infants (birth weight &gt;3 SDs above the reference mean) was 5.61% compared to 2.48% in the nonmacrosomic group (adjusted RR 2.23, 95% CI 1.393.59).</p>
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<h4 class="refs-list-title">Neonatal Complications</h4>
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Boghossian NS, Hansen NI, Bell EF, Brumbaugh JE, Stoll BJ, Laptook AR, Shankaran S, Wyckoff MH, Colaizy TT, Das A, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network: Outcomes of extremely preterm infants born to insulin-dependent diabetic mothers. Pediatrics 137:e20153424, 2016
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href="https://pmc.ncbi.nlm.nih.gov/articles/PMC4894251/"
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<p>U.S. multicenter study of 312 infants of multiethnic mothers using insulin before pregnancy (IBP), delivered at 2228 weeks and cared for at one of 24 NIH Neonatal Research Network hospitals in 20062011; outcomes were compared to 10,245 controls without maternal diabetes. Birth weight extremes for gestational age and sex (Olsen norms) were 10% LGA (NS) and 18% SGA (NS); 5% major birth defects (NS); 15% Apgar score ≤3 at 5 minutes (NS). Rates of morbidities in-hospital in 286 IBP infants surviving &gt;12 hours included 20.6% death before discharge (NS); 99% respiratory distress syndrome (NS); 36% need for supplemental oxygen use at 36 weeks postmenstrual age (NS); 16% severe intraventricular hemorrhage (NS); 3% periventricular leukomalacia (NS); 15% necrotizing enterocolitis (vs. 11%; adjusted RR 1.55, 95% CI 1.172.05); and 35% late-onset sepsis after 3 days (vs. 28%; adjusted RR 1.26, 95% CI 1.071.48). Of 189 IBP infants eligible for follow-up at age 1822 months, there were 37% total deaths between birth and age 1822 months (NS vs. 38% of 6,598 infants eligible for follow-up). Of 109 IBP offspring examined at age 1822 months, 19% had neurodevelopmental impairment (NS vs. 16% of 3,608 controls). There were no data on maternal glycemic control.</p>
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value="1">
Cnattingius S, Lindam A, Persson M: Risks of asphyxia-related neonatal complications in offspring of mothers with type 1 or type 2 diabetes: the impact of maternal overweight and obesity. Diabetologia 60:12441251, 2017
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href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5487600/"
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<p>Population-based study using prospectively collected data on live singleton births of nonmalformed infants from several nationwide Swedish registries for 19972011; 5,941 infants of mothers with type 1 diabetes (IDM1), 711 infants of mothers with type 2 diabetes (IDM2), compared to 1,337,099 infants of mothers without any type of diabetes (controls). Maternal characteristics were: BMI ≥30 kg/m2 in 17.5% of women with type 1 diabetes, 55.5% of women with type 2 diabetes, and 10.7% in controls (excluding women with missing data); smoking in 10.2% of type 1 diabetes, 11.7% of type 2 diabetes, and 9.4% of controls; chronic hypertension in 4.2% of type 1 diabetes, 7.5% of type 2 diabetes, and 0.6% of controls; preeclampsia in 14.2% of type 1 diabetes, 7.6% of type 2 diabetes, and 2.7% in controls; delivery by cesarean section in 50.7% of type 1 diabetes, 42.6% of type 2 diabetes, and 15.1% of controls.</p><p>Neonatal characteristics were: delivery at &lt;32 weeks in 1.8% of IDM1, 2.0% of IDM2, and 0.6% of controls; delivery at 3236 weeks in 17.9% of IDM1, 11.0% of IDM2, and 3.9% of controls; birth weight &lt;third percentile for gestational age in 1.0% of IDM1, 1.3% of IDM2, and 1.5% of controls; birth weight &gt;97th percentile for gestational age in 33.3% of IDM1, 19.8% of IDM2, and 3.4% of controls; Apgar score 06 at 5 minutes in 2.6% of IDM1 (adjusted OR 2.67 compared to controls, 95% CI 2.233.20), 2.1% of IDM2 (NS), and 0.9% of controls; and combined convulsions/hypoxic-ischemic encephalopathy in 1.0% of IDM1 (adjusted OR 3.40 compared to controls, 95% CI 2.584.48), in 1.3% of IDM2 (adjusted OR 2.54 compared to controls, 95% CI 1.135.69), and 0.3% of controls. There was some relation of risk of low Apgar score and neonatal convulsions to increasing maternal BMI in IDM1 and certainly in controls, but the increased rates of the complications in IDM1 remained greater than controls at each maternal BMI grouping. There were no data on maternal glycemic control.</p>
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<h4 class="refs-list-title">Diabetes Management: Maternal Follow-Up</h4>
<ol id="top-references-list-8" class="references-list">
<li>
<ol class="references-and-notes-list">
<li
value="1">
Asbjornsdottir B, Akueson CE, Ronneby H, Rytter A, Andersen JR, Damm P, Mathiesen ER: The influence of carbohydrate consumption on glycemic control in pregnant women with type 1 diabetes. Diabetes Res Clin Pract 127:97104, 2017
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<a
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href="/28340360/"
ref="linksrc=references_link&amp;ordinalpos=1"
data-ga-category="reference"
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PubMed
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<p>Regional study of 80 women with type 1 diabetes who recorded dietary intake for at least 2 days before the first antenatal visit in the Copenhagen, Denmark, area. A1c was positively associated with the quantity of carbohydrate consumed, regardless of type of insulin treatment; 45% of the women used carbohydrate counting daily and had somewhat lower A1c than in those who did not record daily (p=0.01).</p>
</li>
</ol>
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<li>
<ol class="references-and-notes-list">
<li
value="1">
Chico A, Herranz L, Corcoy R, Ramirez O, Goya MM, Bellart J, Gonzalez-Romero S, Codina M, Sanchez P, Cortazar A, Acosta D, Picon MJ, Rubio JA, Megia A, Sancho MA, Balsells M, Sola E, Gonzalez NL, Lopez-Lopez J; GEDE (Group of Diabetes and Pregnancy of the Spanish Diabetes Association): Glycemic control and maternal and fetal outcomes in pregnant women with type 1 diabetes according to the type of basal insulin. Eur J Obstet Gynecol Reprod Biol 206:8491, 2016
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<p>Retrospective cohort study of 1,534 pregnancies at 18 Spanish tertiary hospitals; basal insulin most commonly used was NPH in 51.7% (reference), followed by glargine in 23.2% and CSII in 21.1% (4% missing data). Multiple logistic regression analysis showed that CSII was independently associated with higher A1c in all trimesters and higher rates of miscarriage, preterm birth, and neonatal hypoglycemia; glargine use was related to a higher risk of preterm birth and an SGA infant. Randomized controlled trials are underway elsewhere.</p>
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<li
value="1">
Egan AM, Carmody L, Kirwan B, Dunne FP; Atlantic DIP Collaborators: Care of women with diabetes before, during and after pregnancy: time for a new approach? Diabet Med 34:846850, 2017
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<p>In a multicenter study in West Ireland, 247 women with type 1 diabetes and 137 women with type 2 diabetes were evaluated before, during, and after pregnancy; 20% were lost to 1-year follow-up from clinical care. Average A1c had returned to preconception level for both diabetes groups, and there was no improvement in other measures of diabetes control. Attendees for prepregnancy care (44.9% of type 1 diabetes and 27.7% of type 2 diabetes) maintained superior glycemic control throughout the study and were more likely to be receiving specialist care postpartum.</p>
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<h4 class="refs-list-title">Breastfeeding and Offspring</h4>
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<li
value="1">
Bartick MC, Schwarz EB, Green BD, Jegier BJ, Reinhold AG, Colaizy TT, Bogen DL, Schaefer AJ, Stuebe AM: Suboptimal breastfeeding in the United States: maternal and pediatric health outcomes and costs. Matern Child Nutr 13:e12366, 2017. Jan [Epub] doi: 10.1111/mcn.12366
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<p>Modeled a hypothetical cohort of U.S. women followed from age 15 to 70 years and their children from birth to age 20 years, using Monte Carlo simulations based on current literature on the associations between breastfeeding and health outcomes for nine pediatric and five maternal diseases. For every 597 women who optimally breastfeed, one maternal death (including myocardial infarction, breast cancer, or diabetes) or child death (including sudden infant death syndrome or necrotizing enterocolitis) is prevented.</p>
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Nucci AM, Virtanen SM, Sorkio S, Barlund S, Cuthbertson D, Uusitalo U, Lawson ML, Salonen M, Berseth CL, Ormisson A, Lehtonen E, Savilahti E, Becker DJ, Dupre J, Krischer JP, Knip M, Akerblom HK; TRIGR Investigators: Regional differences in milk and complementary feeding patterns in infants participating in an international nutritional type 1 diabetes prevention trial. Matern Child Nutr 13:e12354, 2017. Jul [Epub] doi: 10.1111/mcn.12354
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<p>Among newborn infants with a first degree relative with type 1 diabetes and increased HLA-conferred susceptibility to type 1 diabetes distributed in four regions of Europe, two of North America, plus Australia, a lower proportion of infants born to mothers with than without type 1 diabetes were breastfed until age 6 months in all regions (range 51%60% vs. 70%80%). Maternal diabetes status was associated with breastfeeding and other milk feeding patterns similarly across regions but was unrelated to the introduction of complementary foods, which did vary by region overall, largely inconsistent with guidelines.</p>
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<li
value="1">
Lund-Blix NA, Dydensborg Sander S, Stordal K, Nybo Andersen AM, Ronningen KS, Joner G, Skrivarhaug T, Nijolstad PR, Husby S, Stene LC: Infant feeding and risk of type 1 diabetes in two large Scandinavian birth cohorts. Diabetes Care 40:920927, 2017
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href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5481976/"
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<p>Analyzed data from 155,392 children participating in Norwegian and Danish studies; parents reported infant dietary practices at ages 6 and 18 months. Children who were never breastfed had a twofold increased risk of type 1 diabetes at follow-up compared with those who were breastfed (HR 2.29, 95% CI 1.144.61). The incidence of type 1 diabetes was independent of duration of full or partial breastfeeding.</p>
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<li
value="1">
Uusitalo U, Liu X, Lang J, Aronsson CA, Hummel S, Butterworth M, Lernmark A, Rewers M, Hagopian W, She JX, Simell O, Toppari J, Ziegler AG, Akolkar B, Krischer J, Norris JM, Virtanen SM; TEDDY Study Group: Association of early exposure to probiotics and islet autoimmunity in the TEDDY Study. JAMA Pediatr 170:2028, 2016
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class="reference-link"
href="https://pmc.ncbi.nlm.nih.gov/articles/PMC4803028/"
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data-ga-action="PMC4803028"
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PMC
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<p>Ongoing prospective cohort follow-up study of 7,473 infants with high-risk HLA (human leukocyte antigen)-DR genotypes at three U.S. and three European centers to determine persistent islet autoimmunity. In children with the DR3/4 genotype, early (age 027 days), but not later, supplementation with varied probiotics by parental report (mainly in Europe; from dietary supplements in Finland and probiotic infant formulas in Germany) was associated with decreased risk of later islet autoimmunity when adjusting for duration of exclusive breastfeeding and many other factors (HR 0.40, 95% CI 0.210.74) and strongly associated with diarrhea and antibiotic use in the first year of life.</p>
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<li
value="1">
Krischer JP, Lynch KF, Lernmark A, Hagopian WA, Rewers MJ, She JX, Toppari J, Ziegler AG, Akolkar B; TEDDY Study Group: Genetic and environmental interactions modify the risk of diabetes-related autoimmunity by 6 years of age: the TEDDY Study. Diabetes Care 40:11941202, 2017
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<p>Infants with HLA-DR high-risk genotypes were prospectively followed for diabetes-related autoantibodies. The persisting GAD (glutamic acid decarboxylase) antibody was associated with only father as the diabetic proband and infant weight at age 12 months; mother as the diabetic proband was not a significant risk factor.</p>
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