<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02189265</url>
  </required_header>
  <id_info>
    <org_study_id>TRF NR-0166-1.3</org_study_id>
    <nct_id>NCT02189265</nct_id>
  </id_info>
  <brief_title>Assessing the Impact of Smoke-free Legislation on Perinatal Health in the Netherlands</brief_title>
  <official_title>Assessing the Impact of Smoke-free Legislation on Perinatal Health in the Netherlands</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Edinburgh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Maastricht University Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Netherlands Perinatal Registry (PRN)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Edinburgh</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate whether there has been a change in perinatal&#xD;
      outcomes following the phased smoking ban introduction (January 2004 for workplaces; July&#xD;
      2008 for bars and restaurants) workplaces in the Netherlands.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary research questions&#xD;
&#xD;
        1. Is the phased introduction of smoke-free legislation in The Netherlands associated with&#xD;
           reductions in adverse perinatal outcomes (e.g. perinatal mortality, preterm birth, small&#xD;
           for gestational age)?&#xD;
&#xD;
        2. How do these associations compare with those described for other European countries in&#xD;
           comparable studies (i.e. Belgium (Cox 2013), England (Been et al under review), Scotland&#xD;
           (Mackay 2012))?&#xD;
&#xD;
      Study design Retrospective cohort study (using prospective routinely collected health care&#xD;
      data)&#xD;
&#xD;
      Study population All singleton births in the Netherlands between January 1st 2000 and&#xD;
      December 31st 2011.&#xD;
&#xD;
      Intervention The intervention under study is the ban on smoking in workplaces, and in bars&#xD;
      and restaurants implemented in the Netherlands on January 1st, 2004 and July 1st, 2008,&#xD;
      respectively.&#xD;
&#xD;
      Inclusion and exclusion criteria We will include all registered singleton births in the&#xD;
      Netherlands occurring between January 1st, 2000 and December 31st, 2011. This is the maximum&#xD;
      time period surrounding the ban's introduction for which the required birth data are&#xD;
      available through the data source. Multiple pregnancies, neonates with chromosomal anomalies,&#xD;
      pregnancies with unknown gestational age, pregnancies that ended before 24 weeks and&#xD;
      pregnancies resulting in the birth of a child weighing less than 500 grams will be excluded.&#xD;
&#xD;
      Outcome&#xD;
&#xD;
      The primary outcomes are:&#xD;
&#xD;
        -  Perinatal mortality (stillbirth + early neonatal mortality, i.e. within the first 7 days&#xD;
           of life)&#xD;
&#xD;
        -  Preterm birth (live birth with gestational age &lt;37+0 weeks)&#xD;
&#xD;
        -  Small for gestational age (SGA; live birth with birth weight below 10th centile; The&#xD;
           Dutch PRN reference curves for birth weight by gestational age according to parity, sex&#xD;
           and ethnic background will be used)&#xD;
&#xD;
      To assess whether smoke-free legislation had a selective impact on certain subgroups of&#xD;
      outcomes we furthermore identified a number of secondary outcomes:&#xD;
&#xD;
        -  Stillbirth (born dead from 24+0 weeks of gestation)&#xD;
&#xD;
        -  Early neonatal mortality (live birth and death within first 7 days)&#xD;
&#xD;
        -  Very preterm birth (live birth with gestational age &lt;32+0 weeks)&#xD;
&#xD;
        -  Low birth weight (live birth with birth weight &lt;2500 grams)&#xD;
&#xD;
        -  Very low birth weight (live birth with birth weight &lt;1500 grams)&#xD;
&#xD;
        -  Very small for gestational age (live birth with birth weight below percentile 2.3rd&#xD;
           centile)&#xD;
&#xD;
        -  Major congenital anomalies (based on reported associations with antenatal smoke exposure&#xD;
           (Hackshaw 2011)).&#xD;
&#xD;
      Data sources Individual level health care data will be extracted from The Netherlands&#xD;
      Perinatal Registry (PRN). Linked midwifery, obstetric, and neonatal data are available from&#xD;
      2000 to 2011 (including 2011).&#xD;
&#xD;
      Data extraction and handling All relevant variables regarding our outcomes, as well as&#xD;
      relevant potential confounders will be extracted from the database.&#xD;
&#xD;
      Sample size Power calculation for interrupted time series modelling is complicated given the&#xD;
      complexity of the analysis. Similar previous studies have demonstrated statistically&#xD;
      significant and clinically relevant effects of smoke-free legislation on preterm birth (Cox&#xD;
      2013; Mackay 2012; Page 2012), low birth weight (Mackay 2012), SGA (Mackay 2012; Kabir 2013),&#xD;
      and perinatal mortality (Mackay et al. and Been et al. both under review). Given the larger&#xD;
      population size of the Netherlands as opposed to the regions in which these studies were&#xD;
      carried out (except for Been et al. under review), we expect our study to have sufficient&#xD;
      power to detect similar effect sizes, should these be present.&#xD;
&#xD;
      Statistical analysis Incidences for each outcome will be presented graphically for each time&#xD;
      period to facilitate visualisation of temporal fluctuations and trends in changes of&#xD;
      incidence levels. To facilitate timing of the events, date of delivery and expected term date&#xD;
      are required for each pregnancy. Data will be presented as outlined in different Tables.&#xD;
      Interrupted time series analyses with adjustment for potential confounders will be performed&#xD;
      to assess the associations between implementation of smoke-free legislation and primary and&#xD;
      secondary outcome measures. Individual-level analysis will be performed using logistic&#xD;
      regression analysis. The models will account for the underlying temporal trend in incidence,&#xD;
      and will allow for a sudden change in incidence ('step change') following the introduction of&#xD;
      the smoking bans. We will test and adjust for any non-linearity in the underlying time&#xD;
      trends, and seasonality will be accounted as appropriate.&#xD;
&#xD;
      Sensitivity analyses (primary outcomes only) In recent years, gestational age is usually&#xD;
      estimated based on early ultrasonography findings, which is more reliable than estimation&#xD;
      based on the last menstrual period. Although the method of ascertainment is not recorded in&#xD;
      PRN, there is an item indicating 'certainty' of the gestational age, which is positive in&#xD;
      about 93% of records. For the primary outcomes preterm birth and SGA we will perform a&#xD;
      sensitivity analysis including only cases in whom gestational age estimation is considered&#xD;
      reliable according to this item.&#xD;
&#xD;
      Recent perinatal management changes have been implemented in The Netherlands resulting in&#xD;
      increased active management of babies born at the edge of viability (i.e. 23-24 weeks&#xD;
      gestation) (NVOG 2010). This has resulted in increased survival at this gestational age as&#xD;
      well as altered management of 25-26 week infants, which likely affects the number of babies&#xD;
      born preterm (although this effect is expected to be small given the small percentage of all&#xD;
      preterm babies being born at this stage), as well as mortality indicators. For the primary&#xD;
      outcomes preterm birth and perinatal mortality we will therefore perform a sensitivity&#xD;
      analysis excluding babies born before 26 completed weeks of gestation.&#xD;
&#xD;
      Smoking during pregnancy is known to be underreported in the PRN database. Definitions&#xD;
      between different caregivers differ; (any) smoking and heavy smoking (&gt;20 cigarettes daily).&#xD;
      We will consider performing subgroup analyses of the impact of smoke-free legislation on the&#xD;
      primary outcomes according to maternal smoking status during pregnancy.&#xD;
&#xD;
      In a sensitivity analysis we will investigate whether smoke-free legislation has any&#xD;
      differential impact on spontaneous preterm birth versus medically indicated preterm birth.&#xD;
&#xD;
      All analyses will be performed using Stata 13.0.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2000</start_date>
  <completion_date type="Actual">July 2014</completion_date>
  <primary_completion_date type="Actual">December 2011</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Ecologic or Community</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Perinatal mortality</measure>
    <time_frame>from 24+0 weeks gestation (for stillbirth); up to 7 days postnatally (for early neonatal mortality)</time_frame>
    <description>stillbirth (i.e. intrauterine death from 24+0 weeks gestation) or early neonatal mortality (i.e. death within the first 7 days postnatally)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Preterm birth</measure>
    <time_frame>gestational age &gt;= 24+0 weeks and &lt;37+0 weeks</time_frame>
    <description>live birth with gestational age &gt;= 24+0 weeks and &lt;37+0 weeks</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Small for gestational age</measure>
    <time_frame>gestational age &gt;= 24+0 weeks</time_frame>
    <description>live birth at gestational age &gt;= 24+0 weeks with birth weight below 10th centile</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Stillbirth</measure>
    <time_frame>gestational age &gt;= 24+0 weeks</time_frame>
    <description>born dead from 24+0 weeks of gestation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Early neonatal mortality</measure>
    <time_frame>up to 7 days postnatally after live birth at gestational age &gt;= 24+0 weeks</time_frame>
    <description>death within first 7 days after live birth at gestational age &gt;= 24+0 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Very preterm birth</measure>
    <time_frame>gestational age &gt;= 24+0 weeks and &lt;32+0 weeks</time_frame>
    <description>live birth with gestational age &gt;= 24+0 weeks and &lt;32+0 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Low birth weight</measure>
    <time_frame>gestational age &gt;= 24+0 weeks</time_frame>
    <description>live birth at gestational age &gt;= 24+0 weeks with birth weight &lt;2500 grams</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Very low birth weight</measure>
    <time_frame>gestational age &gt;= 24+0 weeks</time_frame>
    <description>live birth at gestational age &gt;= 24+0 weeks with birth weight &lt;1500 grams</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Very small for gestational age</measure>
    <time_frame>gestational age &gt;= 24+0 weeks</time_frame>
    <description>live birth at gestational age &gt;= 24+0 weeks with birth weight below 2.3rd centile</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major congenital anomalies</measure>
    <time_frame>gestational age &gt;= 24+0 weeks</time_frame>
    <description>birth at &gt;= 24+0 weeks of gestation with a major birth defect (birth defects known to be influenced by antenatal smoke exposure based on recent systematic review (Hackshaw 2011))</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">2069695</enrollment>
  <condition>Premature Birth</condition>
  <condition>Perinatal Mortality</condition>
  <condition>Infant, Low Birth Weight</condition>
  <condition>Stillbirth</condition>
  <condition>Infant Mortality</condition>
  <condition>Sudden Infant Death</condition>
  <condition>Infant, Very Low Birth Weight</condition>
  <condition>Infant, Small for Gestational Age</condition>
  <arm_group>
    <arm_group_label>Full cohort</arm_group_label>
    <description>All singleton births in the Netherlands. Stillbirths are excluded from the denominator for all outcomes other than perinatal mortality, stillbirth and congenital anomalies.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Smoke-free legislation</intervention_name>
    <description>The intervention under study is the ban on smoking in workplaces, and in bars and restaurants implemented in the Netherlands on January 1st, 2004 and July 1st, 2008, respectively.</description>
    <arm_group_label>Full cohort</arm_group_label>
  </intervention>
  <biospec_descr>
    <textblock>
      None Retained&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        All singleton births in the Netherlands. Stillbirths are excluded from the denominator for&#xD;
        all outcomes other than stillbirths and congenital anomalies.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Data are obtained via The Netherlands Perinatal Registry (PRN) (6). All registered&#xD;
        stillbirths and livebirths occurring in the Netherlands between 1 January 2000 and 31&#xD;
        December 2011 are included.&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Singleton birth occurring in the Netherlands between January 1st, 2000 and December&#xD;
             31st, 2011&#xD;
&#xD;
          -  Liveborn (for all outcomes other than stillbirth and congenital anomalies)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No chromosomal anomalies&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>1 Week</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jasper V Been, MD MPH PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Allergy and Respiratory Research Group, Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Academic Medical Centre</name>
      <address>
        <city>Amsterdam</city>
        <state>Noord Holland</state>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre for Population Health Sciences, The University of Edinburgh</name>
      <address>
        <city>Edinburgh</city>
        <state>Midlothian</state>
        <zip>EH8 9AG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Cox B, Martens E, Nemery B, Vangronsveld J, Nawrot TS. Impact of a stepwise introduction of smoke-free legislation on the rate of preterm births: analysis of routinely collected birth data. BMJ. 2013 Feb 14;346:f441. doi: 10.1136/bmj.f441.</citation>
    <PMID>23412829</PMID>
  </reference>
  <reference>
    <citation>Mackay DF, Nelson SM, Haw SJ, Pell JP. Impact of Scotland's smoke-free legislation on pregnancy complications: retrospective cohort study. PLoS Med. 2012;9(3):e1001175. doi: 10.1371/journal.pmed.1001175. Epub 2012 Mar 6.</citation>
    <PMID>22412353</PMID>
  </reference>
  <reference>
    <citation>Page RL 2nd, Slejko JF, Libby AM. A citywide smoking ban reduced maternal smoking and risk for preterm births: a Colorado natural experiment. J Womens Health (Larchmt). 2012 Jun;21(6):621-7. doi: 10.1089/jwh.2011.3305. Epub 2012 Mar 8.</citation>
    <PMID>22401497</PMID>
  </reference>
  <reference>
    <citation>Kabir Z, Daly S, Clarke V, Keogan S, Clancy L. Smoking ban and small-for-gestational age births in Ireland. PLoS One. 2013;8(3):e57441. doi: 10.1371/journal.pone.0057441. Epub 2013 Mar 26.</citation>
    <PMID>23555561</PMID>
  </reference>
  <reference>
    <citation>Hackshaw A, Rodeck C, Boniface S. Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls. Hum Reprod Update. 2011 Sep-Oct;17(5):589-604. doi: 10.1093/humupd/dmr022. Epub 2011 Jul 11.</citation>
    <PMID>21747128</PMID>
  </reference>
  <reference>
    <citation>de Laat MW, Wiegerinck MM, Walther FJ, Boluyt N, Mol BW, van der Post JA, van Lith JM, Offringa M; Nederlandse Vereniging voor Kindergeneeskunde; Nederlandse Vereniging voor Obstetrie en Gynaecologie. [Practice guideline 'Perinatal management of extremely preterm delivery']. Ned Tijdschr Geneeskd. 2010;154:A2701. Dutch.</citation>
    <PMID>21429260</PMID>
  </reference>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 3, 2014</study_first_submitted>
  <study_first_submitted_qc>July 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 14, 2014</study_first_posted>
  <last_update_submitted>July 11, 2014</last_update_submitted>
  <last_update_submitted_qc>July 11, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 14, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Edinburgh</investigator_affiliation>
    <investigator_full_name>Jasper Been</investigator_full_name>
    <investigator_title>Dr.</investigator_title>
  </responsible_party>
  <keyword>Live birth [MeSH]</keyword>
  <keyword>Infant [MeSH]</keyword>
  <keyword>Infant, newborn [MeSH]</keyword>
  <keyword>Second-hand smoke</keyword>
  <keyword>Tobacco smoke pollution [MeSH]</keyword>
  <keyword>Smoke-free</keyword>
  <keyword>Smoke-free policy [MeSH]</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Premature Birth</mesh_term>
    <mesh_term>Stillbirth</mesh_term>
    <mesh_term>Perinatal Death</mesh_term>
    <mesh_term>Body Weight</mesh_term>
    <mesh_term>Birth Weight</mesh_term>
    <mesh_term>Infant Death</mesh_term>
    <mesh_term>Sudden Infant Death</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02189265
org study id: TRF NR-0166-1.3
nct id: NCT02189265
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
The purpose of this study is to investigate whether there has been a change in perinatal
      outcomes following the phased smoking ban introduction (January 2004 for workplaces; July
      2008 for bars and restaurants) workplaces in the Netherlands.
Primary research questions

        1. Is the phased introduction of smoke-free legislation in The Netherlands associated with
           reductions in adverse perinatal outcomes (e.g. perinatal mortality, preterm birth, small
           for gestational age)?

        2. How do these associations compare with those described for other European countries in
           comparable studies (i.e. Belgium (Cox 2013), England (Been et al under review), Scotland
           (Mackay 2012))?

      Study design Retrospective cohort study (using prospective routinely collected health care
      data)

      Study population All singleton births in the Netherlands between January 1st 2000 and
      December 31st 2011.

      Intervention The intervention under study is the ban on smoking in workplaces, and in bars
      and restaurants implemented in the Netherlands on January 1st, 2004 and July 1st, 2008,
      respectively.

      Inclusion and exclusion criteria We will include all registered singleton births in the
      Netherlands occurring between January 1st, 2000 and December 31st, 2011. This is the maximum
      time period surrounding the ban's introduction for which the required birth data are
      available through the data source. Multiple pregnancies, neonates with chromosomal anomalies,
      pregnancies with unknown gestational age, pregnancies that ended before 24 weeks and
      pregnancies resulting in the birth of a child weighing less than 500 grams will be excluded.

      Outcome

      The primary outcomes are:

        -  Perinatal mortality (stillbirth + early neonatal mortality, i.e. within the first 7 days
           of life)

        -  Preterm birth (live birth with gestational age <37+0 weeks)

        -  Small for gestational age (SGA; live birth with birth weight below 10th centile; The
           Dutch PRN reference curves for birth weight by gestational age according to parity, sex
           and ethnic background will be used)

      To assess whether smoke-free legislation had a selective impact on certain subgroups of
      outcomes we furthermore identified a number of secondary outcomes:

        -  Stillbirth (born dead from 24+0 weeks of gestation)

        -  Early neonatal mortality (live birth and death within first 7 days)

        -  Very preterm birth (live birth with gestational age <32+0 weeks)

        -  Low birth weight (live birth with birth weight <2500 grams)

        -  Very low birth weight (live birth with birth weight <1500 grams)

        -  Very small for gestational age (live birth with birth weight below percentile 2.3rd
           centile)

        -  Major congenital anomalies (based on reported associations with antenatal smoke exposure
           (Hackshaw 2011)).

      Data sources Individual level health care data will be extracted from The Netherlands
      Perinatal Registry (PRN). Linked midwifery, obstetric, and neonatal data are available from
      2000 to 2011 (including 2011).

      Data extraction and handling All relevant variables regarding our outcomes, as well as
      relevant potential confounders will be extracted from the database.

      Sample size Power calculation for interrupted time series modelling is complicated given the
      complexity of the analysis. Similar previous studies have demonstrated statistically
      significant and clinically relevant effects of smoke-free legislation on preterm birth (Cox
      2013; Mackay 2012; Page 2012), low birth weight (Mackay 2012), SGA (Mackay 2012; Kabir 2013),
      and perinatal mortality (Mackay et al. and Been et al. both under review). Given the larger
      population size of the Netherlands as opposed to the regions in which these studies were
      carried out (except for Been et al. under review), we expect our study to have sufficient
      power to detect similar effect sizes, should these be present.

      Statistical analysis Incidences for each outcome will be presented graphically for each time
      period to facilitate visualisation of temporal fluctuations and trends in changes of
      incidence levels. To facilitate timing of the events, date of delivery and expected term date
      are required for each pregnancy. Data will be presented as outlined in different Tables.
      Interrupted time series analyses with adjustment for potential confounders will be performed
      to assess the associations between implementation of smoke-free legislation and primary and
      secondary outcome measures. Individual-level analysis will be performed using logistic
      regression analysis. The models will account for the underlying temporal trend in incidence,
      and will allow for a sudden change in incidence ('step change') following the introduction of
      the smoking bans. We will test and adjust for any non-linearity in the underlying time
      trends, and seasonality will be accounted as appropriate.

      Sensitivity analyses (primary outcomes only) In recent years, gestational age is usually
      estimated based on early ultrasonography findings, which is more reliable than estimation
      based on the last menstrual period. Although the method of ascertainment is not recorded in
      PRN, there is an item indicating 'certainty' of the gestational age, which is positive in
      about 93% of records. For the primary outcomes preterm birth and SGA we will perform a
      sensitivity analysis including only cases in whom gestational age estimation is considered
      reliable according to this item.

      Recent perinatal management changes have been implemented in The Netherlands resulting in
      increased active management of babies born at the edge of viability (i.e. 23-24 weeks
      gestation) (NVOG 2010). This has resulted in increased survival at this gestational age as
      well as altered management of 25-26 week infants, which likely affects the number of babies
      born preterm (although this effect is expected to be small given the small percentage of all
      preterm babies being born at this stage), as well as mortality indicators. For the primary
      outcomes preterm birth and perinatal mortality we will therefore perform a sensitivity
      analysis excluding babies born before 26 completed weeks of gestation.

      Smoking during pregnancy is known to be underreported in the PRN database. Definitions
      between different caregivers differ; (any) smoking and heavy smoking (>20 cigarettes daily).
      We will consider performing subgroup analyses of the impact of smoke-free legislation on the
      primary outcomes according to maternal smoking status during pregnancy.

      In a sensitivity analysis we will investigate whether smoke-free legislation has any
      differential impact on spontaneous preterm birth versus medically indicated preterm birth.

      All analyses will be performed using Stata 13.0.
observational model: Ecologic or Community
time perspective: Retrospective
measure: Perinatal mortality
time frame: from 24+0 weeks gestation (for stillbirth); up to 7 days postnatally (for early neonatal mortality)
description: stillbirth (i.e. intrauterine death from 24+0 weeks gestation) or early neonatal mortality (i.e. death within the first 7 days postnatally)
measure: Preterm birth
time frame: gestational age >= 24+0 weeks and <37+0 weeks
description: live birth with gestational age >= 24+0 weeks and <37+0 weeks
measure: Small for gestational age
time frame: gestational age >= 24+0 weeks
description: live birth at gestational age >= 24+0 weeks with birth weight below 10th centile
measure: Stillbirth
time frame: gestational age >= 24+0 weeks
description: born dead from 24+0 weeks of gestation
measure: Early neonatal mortality
time frame: up to 7 days postnatally after live birth at gestational age >= 24+0 weeks
description: death within first 7 days after live birth at gestational age >= 24+0 weeks
measure: Very preterm birth
time frame: gestational age >= 24+0 weeks and <32+0 weeks
description: live birth with gestational age >= 24+0 weeks and <32+0 weeks
measure: Low birth weight
time frame: gestational age >= 24+0 weeks
description: live birth at gestational age >= 24+0 weeks with birth weight <2500 grams
measure: Very low birth weight
time frame: gestational age >= 24+0 weeks
description: live birth at gestational age >= 24+0 weeks with birth weight <1500 grams
measure: Very small for gestational age
time frame: gestational age >= 24+0 weeks
description: live birth at gestational age >= 24+0 weeks with birth weight below 2.3rd centile
measure: Major congenital anomalies
time frame: gestational age >= 24+0 weeks
description: birth at >= 24+0 weeks of gestation with a major birth defect (birth defects known to be influenced by antenatal smoke exposure based on recent systematic review (Hackshaw 2011))
arm group label: Full cohort
description: All singleton births in the Netherlands. Stillbirths are excluded from the denominator for all outcomes other than perinatal mortality, stillbirth and congenital anomalies.
intervention type: Other
intervention name: Smoke-free legislation
description: The intervention under study is the ban on smoking in workplaces, and in bars and restaurants implemented in the Netherlands on January 1st, 2004 and July 1st, 2008, respectively.
arm group label: Full cohort
None Retained
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 1 Week
healthy volunteers: Accepts Healthy Volunteers
last name: Jasper V Been, MD MPH PhD
role: Principal Investigator
affiliation: Allergy and Respiratory Research Group, Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK
facility: 
facility: 
country: Netherlands
country: United Kingdom
citation: Cox B, Martens E, Nemery B, Vangronsveld J, Nawrot TS. Impact of a stepwise introduction of smoke-free legislation on the rate of preterm births: analysis of routinely collected birth data. BMJ. 2013 Feb 14;346:f441. doi: 10.1136/bmj.f441.
PMID: 23412829
citation: Mackay DF, Nelson SM, Haw SJ, Pell JP. Impact of Scotland's smoke-free legislation on pregnancy complications: retrospective cohort study. PLoS Med. 2012;9(3):e1001175. doi: 10.1371/journal.pmed.1001175. Epub 2012 Mar 6.
PMID: 22412353
citation: Page RL 2nd, Slejko JF, Libby AM. A citywide smoking ban reduced maternal smoking and risk for preterm births: a Colorado natural experiment. J Womens Health (Larchmt). 2012 Jun;21(6):621-7. doi: 10.1089/jwh.2011.3305. Epub 2012 Mar 8.
PMID: 22401497
citation: Kabir Z, Daly S, Clarke V, Keogan S, Clancy L. Smoking ban and small-for-gestational age births in Ireland. PLoS One. 2013;8(3):e57441. doi: 10.1371/journal.pone.0057441. Epub 2013 Mar 26.
PMID: 23555561
citation: Hackshaw A, Rodeck C, Boniface S. Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls. Hum Reprod Update. 2011 Sep-Oct;17(5):589-604. doi: 10.1093/humupd/dmr022. Epub 2011 Jul 11.
PMID: 21747128
citation: de Laat MW, Wiegerinck MM, Walther FJ, Boluyt N, Mol BW, van der Post JA, van Lith JM, Offringa M; Nederlandse Vereniging voor Kindergeneeskunde; Nederlandse Vereniging voor Obstetrie en Gynaecologie. [Practice guideline 'Perinatal management of extremely preterm delivery']. Ned Tijdschr Geneeskd. 2010;154:A2701. Dutch.
PMID: 21429260
responsible party type: Principal Investigator
investigator affiliation: University of Edinburgh
investigator full name: Jasper Been
investigator title: Dr.
mesh term: Premature Birth
mesh term: Stillbirth
mesh term: Perinatal Death
mesh term: Body Weight
mesh term: Birth Weight
mesh term: Infant Death
mesh term: Sudden Infant Death