Using primary care data to assess population-level estimates of maternal smoking and nicotine replacement therapy during pregnancy

Background: Smoking in pregnancy is the most significant preventable cause of poor health outcomes for women and their babies and, therefore, is a major public health concern. In the UK there is a wide range of interventions and support for pregnant women who want to quit. One of these is nicotine replacement therapy (NRT) which has been widely available for retail purchase and prescribing to pregnant women since 2005. However, measures of NRT prescribing in pregnant women are scarce. These measures are vital to assess its usefulness in smoking cessation during pregnancy at a population level. Furthermore, evidence of NRT safety in pregnancy for the mother and child’s health so far is nebulous, with existing studies being small or using retrospectively reported exposures. Aims and Objectives: The main aim of this work was to assess population-level estimates of maternal smoking and NRT prescribing in pregnancy and the safety of NRT for both the mother and the child in the UK. Currently, the only population-level data on UK maternal smoking are from repeated cross-sectional surveys or routinely collected maternity data during pregnancy or at delivery. These obtain information at one point in time, and there are no population-level data on NRT use available. As a novel approach, therefore, this thesis used the routinely collected primary care data that are currently available for approximately 6% of the UK population and provide longitudinal/prospectively recorded information throughout pregnancy. The specific objectives for this thesis were: • To assess the quality of smoking data recorded during pregnancy in primary care • To quantify annual NRT prescribing trends in and around pregnancy and describe the characteristics of mothers prescribed NRT • To assess the association between NRT and smoking exposure during pregnancy and major congenital anomalies (MCAs), stillbirth, low birth weight and mode of delivery Methods: All women aged 15-49 years, with pregnancies ending in live or stillbirth, were identified from The Health Improvement Network (THIN) primary care database (2000-2009). Medical Read codes related to smoking status and Multilex smoking cessation drug prescription codes were used to extract data on women’s smoking status and NRT prescriptions. The proportion of pregnancies with a smoking status record was calculated and logistic regression was used to assess how this varied by women’s characteristics. Women were categorised as being smokers or non-smokers during pregnancy based on the recorded Read codes. Where smoking data were missing during pregnancy, smoking status recorded before pregnancy (up to 27 months before pregnancy, ever before pregnancy) was used as a proxy for smoking status during pregnancy. Annual smoking measures from THIN were then compared to other national datasets. Pregnancies ending in early fetal losses were not included for calculating smoking prevalence, as these outcomes can go unrecognised or can be the first recognised sign of pregnancy, making early ascertainment of all pregnancies uncomprehensive; this was also broadly in line with pregnancy ascertainment in the other national datasets. Prescribing prevalence of NRT and patterns of prescribing in terms of frequency, timing and different form of NRT were assessed. Logistic regression was used to assess women’s likelihood of receiving NRT prescriptions by maternal characteristics. Absolute and relative risks (99% Confidence Interval (CI)) for four birth outcomes (MCAs, stillbirth, low birth weight and mode of delivery) were calculated for women prescribed NRT (defined as the NRT group) and women who continued to smoke during pregnancy (defined as smokers) compared to women who did not smoke during pregnancy (defined as non-smokers) with appropriate adjustments for potential confounders. To assess MCAs and birth weight in relation to NRT and smoking a restricted cohort of children was used who had maternal-child linked records in THIN. Results: There were 277,552 pregnancies in 215,703 women, of which 28% had a gestational smoking status record. In 2000, smoking status was recorded in 9% of pregnancies; 43% in 2009. Smoking estimates from THIN data did not completely agree with estimates from other sources. For example, in 2009 smoking prevalence was 12.9% in THIN, compared to 19.5% in Child Health Systems Programme (CHSP) data. However, the use of smoking data recorded up to 27 months before conception increased the THIN prevalence to 22.9%, which was slightly higher, but compared better with the CHSP estimates. NRT was prescribed in 4,826 pregnancies for an average duration of 2 weeks (Interquartile range 1-2 weeks), which represented 2% of all pregnancies (11% in smokers). NRT prescribing prevalence before and after pregnancy was half the prevalence during pregnancy. NRT prescribing increased with socioeconomic deprivation (Odds Ratio (OR) =1.33, 95% CI 1.14-1.52) for the most compared to the least deprived group). Prescribing was higher in pregnant smokers with asthma (OR=1.34, 95% CI 1.21-1.50) and mental illness (OR=1.29, 95% CI 1.18-1.43) compared to smokers without these diagnoses. The absolute risk of MCA was 279/10,000 live births. Compared with non-smokers the adjusted OR for MCA in the NRT group was 1.34 (99% CI 0.94-1.91). No statistically significant increase in the risk of MCA for the NRT group was found when the reference group was changed to smokers (OR=1.35, 99% CI 0.94-1.93).The absolute risk of stillbirth was 4/1000 live and stillbirths. Compared with non-smokers the adjusted OR for stillbirth in the NRT group was 1.19 (99% CI 0.47-3.01). In smokers, the risk of stillbirth increased by 27% compared to non-smokers (OR 1.27, 99% CI 1.01-1.60). The mean birth weight was 3.41kg (standard deviation 0.59) and the absolute risk of low birth weight was 6.4%. Compared to non-smokers, the risk of women having low birth weight babies was 93% higher in the NRT group (OR 1.93, 99% CI 1.48-2.53). However, there was no statistically significant increase in the risk of low birth weight in the NRT group compared with smokers. There was no increased risk of assisted delivery or caesarean section in the NRT group compared to smokers. However the risk of assisted delivery decreased by 25% in the NRT group (Relative Risk Ratio 0.75, 99% CI 0.60-0.93) compared to non-smokers. Conclusion: The completeness of smoking status recording during pregnancy in primary care data is improving; however, under-recording of smoking status during pregnancy still results in unreliable estimates of the prevalence of smoking in pregnancy and needs improvement. Pre-conception smoking records are reasonably complete and it is possible that low recording in pregnancy is because a woman’s smoking status has not changed or that increased interaction with other health services, such as midwifery, during pregnancy means women are less likely to be asked about their smoking by their primary physician and information on their smoking does not get relayed back to their primary care record. Nevertheless records should be updated in pregnancy to ensure comprehensive health care. NRT was most commonly prescribed in pregnancy for about two weeks, which may not be adequate time for effective smoking cessation. Nevertheless, prescribing was higher during pregnancy compared to the nine months before and after pregnancy, which makes establishing its safety during pregnancy even more crucial. The safety studies in this thesis did not find NRT to be any more harmful than smoking during pregnancy if not beneficial. Considering that smoking in pregnancy remains one of the largest public health problems in the UK, improvements of antenatal and postnatal smoking in primary care may not only help identify women for preventive measures earlier but would be invaluable for safety studies considering the outcomes are rare yet severe

Using primary care data to assess population-level estimates of maternal smoking and nicotine replacement therapy during pregnancy

Background: Smoking in pregnancy is the most significant preventable cause of poor health outcomes for women and their babies and, therefore, is a major public health concern. In the UK there is a wide range of interventions and support for pregnant women who want to quit. One of these is nicotine replacement therapy (NRT) which has been widely available for retail purchase and prescribing to pregnant women since 2005. However, measures of NRT prescribing in pregnant women are scarce. These measures are vital to assess its usefulness in smoking cessation during pregnancy at a population level. Furthermore, evidence of NRT safety in pregnancy for the mother and child’s health so far is nebulous, with existing studies being small or using retrospectively reported exposures. Aims and Objectives: The main aim of this work was to assess population-level estimates of maternal smoking and NRT prescribing in pregnancy and the safety of NRT for both the mother and the child in the UK. Currently, the only population-level data on UK maternal smoking are from repeated cross-sectional surveys or routinely collected maternity data during pregnancy or at delivery. These obtain information at one point in time, and there are no population-level data on NRT use available. As a novel approach, therefore, this thesis used the routinely collected primary care data that are currently available for approximately 6% of the UK population and provide longitudinal/prospectively recorded information throughout pregnancy. The specific objectives for this thesis were: • To assess the quality of smoking data recorded during pregnancy in primary care • To quantify annual NRT prescribing trends in and around pregnancy and describe the characteristics of mothers prescribed NRT • To assess the association between NRT and smoking exposure during pregnancy and major congenital anomalies (MCAs), stillbirth, low birth weight and mode of delivery Methods: All women aged 15-49 years, with pregnancies ending in live or stillbirth, were identified from The Health Improvement Network (THIN) primary care database (2000-2009). Medical Read codes related to smoking status and Multilex smoking cessation drug prescription codes were used to extract data on women’s smoking status and NRT prescriptions. The proportion of pregnancies with a smoking status record was calculated and logistic regression was used to assess how this varied by women’s characteristics. Women were categorised as being smokers or non-smokers during pregnancy based on the recorded Read codes. Where smoking data were missing during pregnancy, smoking status recorded before pregnancy (up to 27 months before pregnancy, ever before pregnancy) was used as a proxy for smoking status during pregnancy. Annual smoking measures from THIN were then compared to other national datasets. Pregnancies ending in early fetal losses were not included for calculating smoking prevalence, as these outcomes can go unrecognised or can be the first recognised sign of pregnancy, making early ascertainment of all pregnancies uncomprehensive; this was also broadly in line with pregnancy ascertainment in the other national datasets. Prescribing prevalence of NRT and patterns of prescribing in terms of frequency, timing and different form of NRT were assessed. Logistic regression was used to assess women’s likelihood of receiving NRT prescriptions by maternal characteristics. Absolute and relative risks (99% Confidence Interval (CI)) for four birth outcomes (MCAs, stillbirth, low birth weight and mode of delivery) were calculated for women prescribed NRT (defined as the NRT group) and women who continued to smoke during pregnancy (defined as smokers) compared to women who did not smoke during pregnancy (defined as non-smokers) with appropriate adjustments for potential confounders. To assess MCAs and birth weight in relation to NRT and smoking a restricted cohort of children was used who had maternal-child linked records in THIN. Results: There were 277,552 pregnancies in 215,703 women, of which 28% had a gestational smoking status record. In 2000, smoking status was recorded in 9% of pregnancies; 43% in 2009. Smoking estimates from THIN data did not completely agree with estimates from other sources. For example, in 2009 smoking prevalence was 12.9% in THIN, compared to 19.5% in Child Health Systems Programme (CHSP) data. However, the use of smoking data recorded up to 27 months before conception increased the THIN prevalence to 22.9%, which was slightly higher, but compared better with the CHSP estimates. NRT was prescribed in 4,826 pregnancies for an average duration of 2 weeks (Interquartile range 1-2 weeks), which represented 2% of all pregnancies (11% in smokers). NRT prescribing prevalence before and after pregnancy was half the prevalence during pregnancy. NRT prescribing increased with socioeconomic deprivation (Odds Ratio (OR) =1.33, 95% CI 1.14-1.52) for the most compared to the least deprived group). Prescribing was higher in pregnant smokers with asthma (OR=1.34, 95% CI 1.21-1.50) and mental illness (OR=1.29, 95% CI 1.18-1.43) compared to smokers without these diagnoses. The absolute risk of MCA was 279/10,000 live births. Compared with non-smokers the adjusted OR for MCA in the NRT group was 1.34 (99% CI 0.94-1.91). No statistically significant increase in the risk of MCA for the NRT group was found when the reference group was changed to smokers (OR=1.35, 99% CI 0.94-1.93).The absolute risk of stillbirth was 4/1000 live and stillbirths. Compared with non-smokers the adjusted OR for stillbirth in the NRT group was 1.19 (99% CI 0.47-3.01). In smokers, the risk of stillbirth increased by 27% compared to non-smokers (OR 1.27, 99% CI 1.01-1.60). The mean birth weight was 3.41kg (standard deviation 0.59) and the absolute risk of low birth weight was 6.4%. Compared to non-smokers, the risk of women having low birth weight babies was 93% higher in the NRT group (OR 1.93, 99% CI 1.48-2.53). However, there was no statistically significant increase in the risk of low birth weight in the NRT group compared with smokers. There was no increased risk of assisted delivery or caesarean section in the NRT group compared to smokers. However the risk of assisted delivery decreased by 25% in the NRT group (Relative Risk Ratio 0.75, 99% CI 0.60-0.93) compared to non-smokers. Conclusion: The completeness of smoking status recording during pregnancy in primary care data is improving; however, under-recording of smoking status during pregnancy still results in unreliable estimates of the prevalence of smoking in pregnancy and needs improvement. Pre-conception smoking records are reasonably complete and it is possible that low recording in pregnancy is because a woman’s smoking status has not changed or that increased interaction with other health services, such as midwifery, during pregnancy means women are less likely to be asked about their smoking by their primary physician and information on their smoking does not get relayed back to their primary care record. Nevertheless records should be updated in pregnancy to ensure comprehensive health care. NRT was most commonly prescribed in pregnancy for about two weeks, which may not be adequate time for effective smoking cessation. Nevertheless, prescribing was higher during pregnancy compared to the nine months before and after pregnancy, which makes establishing its safety during pregnancy even more crucial. The safety studies in this thesis did not find NRT to be any more harmful than smoking during pregnancy if not beneficial. Considering that smoking in pregnancy remains one of the largest public health problems in the UK, improvements of antenatal and postnatal smoking in primary care may not only help identify women for preventive measures earlier but would be invaluable for safety studies considering the outcomes are rare yet severe

Educational weight loss interventions in obese and overweight adults with type 2 diabetes : a systematic review and meta‐analysis of randomized controlled trials

Aim The worldwide prevalence of type 2 diabetes mellitus is increasing, with most individuals with the disease being overweight or obese. Weight loss can reduce disease‐related morbidity and mortality and weight losses of 10–15 kg have been shown to reverse type 2 diabetes. This review aimed to determine the effectiveness of community‐based educational interventions for weight loss in type 2 diabetes. Methods This is a systematic review and meta‐analysis of randomized controlled trials (RCT) in obese or overweight adults, aged 18–75 years, with a diagnosis of type 2 diabetes. Primary outcomes were weight and/or BMI. CINAHL, MEDLINE, Embase, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to June 2019. Trials were classified into specified a priori comparisons according to intervention type. A pooled standardized mean difference (SMD) (from baseline to follow‐up) and 95% confidence intervals (95% CI) between trial groups (difference‐in‐difference) were estimated through random‐effects meta‐analyses using the inverse variance method. Heterogeneity was quantified using I2 and publication bias was explored visually using funnel plots. Results Some 7383 records were screened; 228 full‐text articles were assessed and 49 RCTs (n = 12 461 participants) were included in this review, with 44 being suitable for inclusion into the meta‐analysis. Pooled estimates of education combined with low‐calorie, low‐carbohydrate meal replacements (SMD = –2.48, 95% CI –3.59, –1.49, I2 = 98%) or diets (SMD = –1.25, 95% CI –2.11, –0.39, I2 = 95%) or low‐fat meal replacements (SMD = –1.15, 95%CI –2.05, –1.09, I2 = 85%) appeared most effective. Conclusion Low‐calorie, low‐carbohydrate meal replacements or diets combined with education appear the most promising interventions to achieve the largest weight and BMI reductions in people with type 2 diabetes

A comparison of United Kingdom primary care data with other national data sources for monitoring the prevalence of smoking during pregnancy

Background: We aimed to assess the potential usefulness of primary care data for estimating smoking prevalence in pregnancy by comparing the primary care data estimates with those obtained from other data sources. Methods: In The Health Improvement Network (THIN) primary care database we identified pregnant smokers using smoking information recorded during pregnancy. Where this information was missing, we used smoking information recorded prior to pregnancy. We compared annual smoking prevalence from 2000 to 2012 in THIN with measures from the Infant Feeding Survey (IFS), Smoking At Time of Delivery (SATOD), Child Health Systems Programme (CHSP) and Scottish Morbidity Record (SMR). Results: Smoking estimates from THIN data converged with estimates from other sources after 2004, though still do not agree completely. For example, in 2012 smoking prevalence at booking was 11.6% in THIN using data recorded only during pregnancy, compared to 19.6% in SMR data. However, the use of smoking data recorded up to 27 months before conception increased the THIN prevalence to 20.3%, improving the agreement. Conclusion: Under-recording of smoking status during pregnancy results in unreliable prevalence estimates from primary care data and needs improvement. However, the inclusion of pre-conception smoking records may increase the utility of primary care data

Long-term persistence with evolocumab treatment and sustained reductions in LDL-cholesterol levels over 30 months: final results from the European observational HEYMANS study

BACKGROUND AND AIMS: Variability in low-density lipoprotein-cholesterol (LDL-C) level control at a population level is associated with poor cardiovascular outcomes. Limited data exist on LDL-C level variability or long-term persistence with the monoclonal antibody evolocumab in routine clinical practice. Using data from the HEYMANS registry, this analysis aimed to assess evolocumab persistence and discontinuation over 30 months of evolocumab treatment and to evaluate at a population level the variability in LDL-C level reductions during the study period. METHODS: HEYMANS was a prospective registry of adults initiating evolocumab in routine clinical practice in 12 European countries. Data were collected for up to and including 6 months before evolocumab initiation and up to 30 months after. Evolocumab discontinuation was analysed for two time periods: 0-12 months and 12-30 months. RESULTS: In total, 1951 patients were included in the study. The median reduction in LDL-C levels was 58% within 3 months after evolocumab initiation; this reduction was maintained over 30 months. More than 90% of patients continued receiving evolocumab at 12 months and 30 months of follow-up. Of patients with an LDL-C level measurement during follow-up, approximately 85% achieved a ≥30% reduction from baseline at each follow-up visit and approximately 60% achieved a ≥50% reduction. CONCLUSIONS: Evolocumab therapy was associated with sustained LDL-C level reductions up to 30 months, and persistence with evolocumab remained high, both at 12 and 30 months. Expanding the use of monoclonal antibodies such as evolocumab could provide improvements in LDL-C level control at a population level in European clinical practice

Pregnancy complications and adverse birth outcomes among women with celiac disease: a population-based study from England

OBJECTIVES: Evidence-based information about adverse birth outcomes and pregnancy complications is crucial when counseling women with celiac disease (CD); however, limited population-based data on such risks exist. We estimated these for pregnant women with CD diagnosed before and after delivery. METHODS: We included all singleton pregnancies between 1997 and 2012 using linked primary care data from the Clinical Practice Research Datalink and secondary care Hospital Episode Statistics data. Risks of pregnancy complications (antepartum and postpartum hemorrhage, pre-eclampsia, and mode of delivery) and adverse birth outcomes (preterm birth, stillbirth, and low birth weight) were compared between pregnancies of women with and without CD using logistic/multinomial regression. Risks were stratified on the basis of whether women were diagnosed or yet undiagnosed before delivery. RESULTS: Of 363,930 pregnancies resulting in a live birth or stillbirth, 892 (0.25%) were among women with CD. Diagnosed CD was not associated with an increased risk of pregnancy complications or adverse birth outcomes compared with women without CD. However, the risk of postpartum hemorrhage and assisted delivery was slightly higher among pregnant women with diagnosed CD (adjusted odds ratio (aOR)=1.34). We found no increased risk of any pregnancy complication among those with undiagnosed CD. We only observed a 1% absolute excess risk of preterm birth and low birth weight among undiagnosed CD mothers corresponding to aOR=1.24 (95% confidence interval (CI)=0.82–1.87) and aOR=1.36 (95% CI=0.83–2.24), respectively. CONCLUSIONS: Whether diagnosed or undiagnosed during pregnancy, CD is not associated with a major increased risk of pregnancy complications and adverse birth outcomes. These findings are reassuring to both women and clinicians

Nicotine replacement therapy in pregnancy and major congenital anomalies in offspring

BACKGROUND AND OBJECTIVES: Nicotine replacement therapy (NRT) is now being used as a smoking cessation aid during pregnancy, although little is known about fetal safety. We assessed the relationship between early pregnancy exposure to NRT or smoking with major congenital anomalies (MCA) in offspring. METHODS: We studied 192 498 children born in the United Kingdom between 2001 and 2012 with linked mother–child primary care records. The absolute risks of MCAs in the NRT group (women prescribed NRT during the first trimester or 1 month before conception [and therefore likely consumed during the first trimester]) and odds ratios (ORs) and 99% confidence intervals (CIs) were compared with those of women who smoked during pregnancy and with a control group (women who neither smoked nor were prescribed NRT); logistic regression models adjusted for maternal morbidities that increase MCA risk were used for analysis. RESULTS: MCA prevalence was 288 per 10 000 live births (5535 children with ≥1 MCA). Maternal morbidities were most common in the NRT group (35%) followed by smokers (27%) and the control group (20%). Compared with the control group, adjusted ORs for MCAs in the NRT group and smokers were 1.12 (99% CI: 0.84–1.48) and 1.05 (99% CI: 0.89–1.23), respectively. The OR comparing the NRT group directly with smokers was 1.07 (99% CI: 0.78–1.47). There were no statistically significant associations between maternal NRT and system-specific anomalies except for respiratory anomalies (OR: 4.65 [99% CI: 1.76–12.25]; absolute risk difference: 3 per 1000 births), which was based on 10 exposed cases. CONCLUSIONS: For most system-specific MCAs, we found no statistically significant increased risks associated with maternal NRT prescribed during pregnancy, except for respiratory anomalies. Although this study is the largest published to date, NRT use in pregnancy remains rare; thus, the statistical power was limited. Higher morbidities in those women prescribed NRT may also be an explanatory factor. Nevertheless, absolute MCA risks were similar between women who smoked and those prescribed NRT during pregnancy

Longitudinal cohort survey of women's smoking behaviour and attitudes in pregnancy: study methods and baseline data.

OBJECTIVES: To report the methods used to assemble a contemporary pregnancy cohort for investigating influences on smoking behaviour before, during and after pregnancy and to report characteristics of women recruited. DESIGN: Longitudinal cohort survey. SETTING: Two maternity hospitals, Nottingham, England. PARTICIPANTS: 3265 women who attended antenatal ultrasound scan clinics were offered cohort enrolment; those who were 8-26 weeks pregnant and were currently smoking or had recently stopped smoking were eligible. Cohort enrollment took place between August 2011 and August 2012. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence of smoking at cohort entry and at two follow-up time points (34-36 weeks gestation and 3 months postnatally); response rate, participants' sociodemographic characteristics. RESULTS: 1101 (33.7%, 95% CI 32.1% to 35.4%) women were eligible for inclusion in the cohort, and of these 850 (77.2%, 95% CI 74.6% to 79.6%) were recruited. Within the cohort, 57.4% (N=488, 95% CI 54.1% to 60.7%) reported to be current smokers. Current smokers were significantly younger than ex-smokers (p<0.05), more likely to have no formal qualifications and to not be in current paid employment compared to recent ex-smokers (p<0.001). CONCLUSIONS: This contemporary cohort, which seeks very detailed information on smoking in pregnancy and its determinants, includes women with comparable sociodemographic characteristics to those in other UK cross-sectional studies and cohorts. This suggests that future analyses using this cohort and aimed at understanding smoking behaviour in pregnancy may produce findings that are broadly generalisable

Association between lifestyle factors and the incidence of multimorbidity in an older English population.

Background: Evidence on the role of lifestyle factors in relation to multimorbidity, especially in elderly populations, is scarce. We assessed the association between five lifestyle factors and incident multimorbidity (presence of ≥2 chronic conditions) in an English cohort aged ≥50 years. Methods: We used data from wave 4, 5 and 6 of the English Longitudinal Study of Ageing. Data on smoking, alcohol consumption, physical activity, fruit and vegetable consumption and BMI were extracted and combined to generate a sum of unhealthy lifestyle factors for each individual. We examined whether these lifestyle factors individually or in combination predicted during the subsequent wave. We used marginal structural Cox proportional hazard models, adjusted for both time-constant and time-varying factors. Results: A total of 5,476 participants contributed 232,749 person-months of follow-up during which 1,156 cases of incident multimorbidity were recorded. Physical inactivity increased the risk of multimorbidity by 33% (adjusted Hazard Ratio (aHR) 1.33, 95% CI 1.03-1.73). The risk was about two-three times higher when inactivity was combined with obesity (aHR 2.87, 95% CI 1.55-5.31) or smoking (aHR 2.35, 95% CI 1.36-4.08) and about four times when combined with both (aHR 3.98, 95% CI 1.02-17.00). Any combination of 2, 3 and 4 or more unhealthy lifestyle factors significantly increased the multimorbidity hazard, compared to none, from 42% to 114%. Conclusion: This study provides evidence of a temporal association between combinations of different unhealthy lifestyle factors with multimorbidity. Population level interventions should include reinforcing positive lifestyle changes in the population to reduce the risk of developing multimorbidity

Women with celiac disease present with fertility problems no more often than women in the general population

BACKGROUND & AIMS: Studies have associated infertility with celiac disease. However, these included small numbers of women attending infertility specialist services and subsequently screened for celiac disease, and therefore may not have been representative of the general population. We performed a large population-based study of infertility and celiac disease in women from the United Kingdom. METHODS: We identified 2,426,225 women with prospective UK primary care records between 1990 and 2013 during their child-bearing years from The Health Improvement Network database. We estimated age-specific rates of new clinically recorded fertility problems among women with and without diagnosed celiac disease. Rates were stratified by whether celiac disease was diagnosed before the fertility problem or afterward and compared with rates in women without celiac disease using Poisson regression, adjusting for sociodemographics, comorbidities, and calendar time. RESULTS: Age-specific rates of new clinically recorded fertility problems in 6506 women with celiac disease were similar to the rates in women without celiac disease (incidence rate ratio, 1.12; 95% confidence interval, 0.88-1.42 among women age 25-29 years). Rates of infertility among women without celiac disease were similar to those of women with celiac disease before and after diagnosis. However, rates were 41% higher among women diagnosed with celiac disease when they were 25-29 years old, compared with women in the same age group without celiac disease (incidence rate ratio, 1.41; 95% confidence interval, 1.03-1.92). CONCLUSIONS: Women with celiac disease do not have a greater likelihood of clinically recorded fertility problems than women without celiac disease, either before or after diagnosis, except for higher reports of fertility problems between 25-39 years if diagnosed with CD. These findings should assure most women with celiac disease that they do not have an increased risk for fertility problems