Assessing the Impact of Smoke-free Legislation on Perinatal Health in the Netherlands

Premature Birth Clinical Trial

Official title:

Assessing the Impact of Smoke-free Legislation on Perinatal Health in the Netherlands

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02189265
• Other study ID #: TRF NR-0166-1.3
• Status: Completed
• Phase: N/A
• First received: July 3, 2014
• Last updated: July 11, 2014
• Start date: January 2000
• Est. completion date: July 2014

Study information

• Verified date: July 2014
• Source: University of Edinburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Ministry of Health, Welfare and Sport
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2069695
• Est. completion date: July 2014
• Est. primary completion date: December 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A to 1 Week

Eligibility

Data are obtained via The Netherlands Perinatal Registry (PRN) (6). All registered stillbirths and livebirths occurring in the Netherlands between 1 January 2000 and 31 December 2011 are included.

Inclusion Criteria:

• Singleton birth occurring in the Netherlands between January 1st, 2000 and December 31st, 2011

• Liveborn (for all outcomes other than stillbirth and congenital anomalies)

Exclusion Criteria:

• No chromosomal anomalies

Study Design

Observational Model: Ecologic or Community, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Birth Weight
• Infant Mortality
• Infant, Low Birth Weight
• Infant, Small for Gestational Age
• Infant, Very Low Birth Weight
• Perinatal Mortality
• Premature Birth
• Stillbirth
• Sudden Infant Death

Intervention

Other:
• Smoke-free legislation
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.

Locations

Country	Name	City	State
Netherlands	Academic Medical Centre	Amsterdam	Noord Holland
United Kingdom	Centre for Population Health Sciences, The University of Edinburgh	Edinburgh	Midlothian

Sponsors (4)

Lead Sponsor	Collaborator
University of Edinburgh	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Maastricht University Medical Center, The Netherlands Perinatal Registry (PRN)

Countries where clinical trial is conducted

Netherlands,  United Kingdom, 

References & Publications (6)

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. — View 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. — View 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. Review. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Perinatal mortality	stillbirth (i.e. intrauterine death from 24+0 weeks gestation) or early neonatal mortality (i.e. death within the first 7 days postnatally)	from 24+0 weeks gestation (for stillbirth); up to 7 days postnatally (for early neonatal mortality)	No
Primary	Preterm birth	live birth with gestational age >= 24+0 weeks and <37+0 weeks	gestational age >= 24+0 weeks and <37+0 weeks	No
Primary	Small for gestational age	live birth at gestational age >= 24+0 weeks with birth weight below 10th centile	gestational age >= 24+0 weeks	No
Secondary	Stillbirth	born dead from 24+0 weeks of gestation	gestational age >= 24+0 weeks	No
Secondary	Early neonatal mortality	death within first 7 days after live birth at gestational age >= 24+0 weeks	up to 7 days postnatally after live birth at gestational age >= 24+0 weeks	No
Secondary	Very preterm birth	live birth with gestational age >= 24+0 weeks and <32+0 weeks	gestational age >= 24+0 weeks and <32+0 weeks	No
Secondary	Low birth weight	live birth at gestational age >= 24+0 weeks with birth weight <2500 grams	gestational age >= 24+0 weeks	No
Secondary	Very low birth weight	live birth at gestational age >= 24+0 weeks with birth weight <1500 grams	gestational age >= 24+0 weeks	No
Secondary	Very small for gestational age	live birth at gestational age >= 24+0 weeks with birth weight below 2.3rd centile	gestational age >= 24+0 weeks	No
Secondary	Major congenital anomalies	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))	gestational age >= 24+0 weeks	No