Clinical management of nausea and vomiting in pregnancy and hyperemesis gravidarum across primary and secondary care: a population-based study.

OBJECTIVES: To assess how nausea and vomiting in pregnancy (NVP) and hyperemesis gravidarum (HG) are managed and treated across primary and secondary care. DESIGN: Population-based pregnancy cohort. SETTING: Medical records (CPRD-GOLD) from England. POPULATION: 417 028 pregnancies during 1998-2014. METHODS: Proportions of pregnancies with recorded NVP/HG diagnoses, primary care treatment, and hospital admissions were calculated. Multinomial logistic regression was employed to estimate adjusted relative risk ratios (aRRRs) with 99% confidence intervals (CIs) for the association between NVP/HG management paths and maternal characteristics. MAIN OUTCOME MEASURES: NVP/HG diagnoses, treatments, and hospital admissions. RESULTS: Overall prevalence of clinically recorded NVP/HG was 9.1%: 2.1% had hospital admissions, 3.4% were treated with antiemetics in primary care only, and 3.6% had only recorded diagnoses. Hospital admissions and antiemetic prescribing increased continuously during 1998-2013 (trend P < 0.001). Younger age, deprivation, Black/Asian/mixed ethnicity, and multiple pregnancy were associated with NVP/HG generally across all levels, but associations were strongest for hospital admissions. Most comorbidities had patterns of association with NVP/HG levels. Among women with NVP/HG who had no hospital admissions, 49% were prescribed antiemetics, mainly from first-line treatment (21% prochlorperazine, 15% promethazine, 13% cyclizine) and metoclopramide (10%). Of those admitted, 38% had prior antiemetic prescriptions (34% first-line, 9% second-line, 1% third-line treatment). CONCLUSION: Previous focus on hospital admissions has greatly underestimated the NVP/HG burden. Although primary care prescribing has increased, most women admitted to hospital have no antiemetics prescribed before this. An urgent call is made to assess whether admissions could be prevented with better primary care recognition and timely treatment. TWEETABLE ABSTRACT: The NVP/HG burden is increasing over time and management optimisation should be high priority to help reduce hospital admissions.

Hospital admission for hyperemesis gravidarum: a nationwide study of occurrence, reoccurrence and risk factors among 8.2 million pregnancies.

STUDY QUESTION: What are the maternal risk factors for hyperemesis gravidarum (HG) hospital admission, readmission and reoccurrence in a following pregnancy? SUMMARY ANSWER: Young age, less socioeconomic deprivation, nulliparity, Asian or Black ethnicity, female fetus, multiple pregnancy, history of HG in a previous pregnancy, thyroid and parathyroid dysfunction, hypercholesterolemia and Type 1 diabetes are all risk factors for HG. WHAT IS KNOWN ALREADY: Women with Black or Asian ethnicity, of young age, carrying multiple babies or singleton females, with Type 1 diabetes or with a history of HG were previously reported to be at higher risk of developing HG; however, most evidence is from small studies. Little is known about associations with other comorbidities and there is controversy over other risk factors such as parity. Estimates of HG prevalence vary and there is a little understanding of the risks of HG readmission in a current pregnancy and reoccurrence rates in subsequent pregnancies, all of which are needed for planning measures to reduce onset or worsening of the condition. STUDY DESIGN, SIZE, DURATION: We performed a population-based cohort study of pregnancies ending in live births and stillbirths using prospectively recorded secondary care records (Hospital Episode Statistics) from England. We analysed those computerized and anonymized clinical records from over 5.3 million women who had one or more pregnancies between 1997 and 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: We obtained 8 215 538 pregnancies from 5 329 101 women of reproductive age, with a total of 186 800 HG admissions occurring during 121 885 pregnancies. Multivariate logistic regression with generalized estimating equations was employed to estimate odds ratios (aOR) to assess sociodemographic, pregnancy and comorbidity risk factors for HG onset, HG readmission within a pregnancy and reoccurrence in a subsequent pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: Being younger, from a less socioeconomically deprived status, of Asian or Black ethnicity, carrying a female fetus or having a multiple pregnancy all significantly increased HG and readmission risk but only ethnicity increased reoccurrence. Comorbidities most strongly associated with HG were parathyroid dysfunction (aOR = 3.83, 95% confidence interval 2.28-6.44), hypercholesterolemia (aOR = 2.54, 1.88-3.44), Type 1 diabetes (aOR = 1.95, 1.82-2.09), and thyroid dysfunction (aOR = 1.85, 1.74-1.96). History of HG was the strongest independent risk factor (aOR = 4.74, 4.46-5.05). Women with higher parity had a lower risk of HG compared with nulliparous women (aOR = 0.90, 0.89-0.91), which was not explained by women with HG curtailing further pregnancies. LIMITATIONS, REASONS FOR CAUTION: Although this represents the largest population-based study worldwide on the topic, the results could have been biased by residual and unmeasured confounding considering that some potential important risk factors such as smoking, BMI or prenatal care could not be measured with these data. Underestimation of non-routinely screened comorbidities such as hypercholesterolemia or thyroid dysfunction could also be a cause of selection bias. WIDER IMPLICATIONS OF THE FINDINGS: The estimated prevalence of 1.5% from our study was similar to the average prevalence reported in the literature and the representativeness of our data has been validated by comparison to national statistics. Also the prevalence of comorbidities was mostly similar to other studies estimating these in the UK and other developed countries. Women with Black or Asian ethnicity, of young age, carrying multiple babies or singleton females, with Type 1 diabetes or with history of HG were confirmed to be at higher risk of HG with an unprecedented higher statistical power. We showed for the first time that socioeconomic status interacts with maternal age, that hypercholesterolemia is a potential risk factor for HG and that carrying multiple females increases risk of hyperemesis compared with multiple males. We also provided robust evidence for the association of parity with HG. Earlier recognition and management of symptoms via gynaecology day-case units or general practitioner services can inform prevention and control of consequent hospital admissions. STUDY FUNDING/COMPETING INTERESTS: The work was founded by The Rosetrees Trust and the Stoneygate Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. C.N.-P. reports personal fees from Sanofi Aventis, Warner Chilcott, Leo Pharma, UCB and Falk, outside the submitted work and she is one of the co-developers of the RCOG Green Top Guideline on HG; all other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Decreased fertility rates in 9639 women diagnosed with inflammatory bowel disease: a United Kingdom population-based cohort study.

BACKGROUND: Clinical studies have reported reduced fertility in women with inflammatory bowel disease (IBD). AIM: To compare fertility rates in women with IBD to those in women without IBD and assess whether the relative fertility differed following IBD diagnosis, flares and surgery. METHODS: Women aged 15-44 years in 1990-2010 were identified from a UK primary care database. We estimated overall and age-specific fertility rates by 5-year age bands for women with and without IBD. We used Poisson regression to calculate adjusted fertility rate ratios (AFRR), adjusted for age, smoking and socioeconomic deprivation. RESULTS: There were 46.2 live births per 1000 person-years [95% confidence interval (95% CI); 44.6-47.9] in 9639 women with IBD and 49.3 (95% CI 49.2-49.5) in 2 131 864 without (AFRR: 0.93; 95% CI: 0.89-0.96). Excluding periods of contraception use, the AFRR was 0.99 (95% CI: 0.95-1.03). Before diagnosis, the AFRR for women with ulcerative colitis (UC) was 1.07 (95% CI: 0.99-1.16) and was 0.88 (95% CI: 0.81-0.97) for women with CD. After diagnosis, AFRRs were 0.87 (95% CI: 0.82-0.94) for CD and 0.92 (95% CI: 0.86-1.00) for UC. The fertility rate was lower following flares (AFRR: 0.70; 95% CI: 0.59-0.82) or surgery (AFRR: 0.84; 95% CI: 0.77-0.92). Women with pouch and non-pouch surgery had similar overall fertility though the reduction after surgery was greater for pouches (AFRR: 0.48; 95% CI: 0.23-0.99). CONCLUSIONS: Women with Crohn's disease have marginally lower fertility rates. These rates decreased following flares and surgical interventions. Fertility rates returned almost to normal when women were not prescribed contraception but the reduction following surgical intervention remained. As the lifetime effect of pouch vs. nonpouch surgery on fertility is small, the reduction post-pouch surgery should be interpreted with caution.

Maternal depression, antidepressant prescriptions, and congenital anomaly risk in offspring: a population-based cohort study.

OBJECTIVE: To estimate risks of major congenital anomaly (MCA) among children of mothers prescribed antidepressants during early pregnancy or diagnosed with depression but without antidepressant prescriptions. DESIGN: Population-based cohort study. SETTING: Linked UK maternal-child primary care records. POPULATION: A total of 349,127 singletons liveborn between 1990 and 2009. METHODS: Odds ratios adjusted for maternal sociodemographics and comorbidities (aORs) were calculated for MCAs, comparing women with first-trimester selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs) and women with diagnosed but unmedicated depression, or women without diagnosed depression. MAIN OUTCOME MEASURES: Fourteen system-specific MCA groups classified according to the European Surveillance of Congenital Anomalies and five specific heart anomaly groups. RESULTS: Absolute risks of MCA were 2.7% (95% confidence interval, 95% CI, 2.6-2.8%) in children of mothers without diagnosed depression, 2.8% (95% CI 2.5-3.2%) in children of mothers with unmedicated depression, and 2.7% (95% CI 2.2-3.2%) and 3.1% (95% CI 2.2-4.1%) in children of mothers with SSRIs or TCAs, respectively. Compared with women without depression, MCA overall was not associated with unmedicated depression (aOR 1.07, 95% CI 0.96-1.18), SSRIs (aOR 1.01, 95% CI 0.88-1.17), or TCAs (aOR 1.09, 95% CI 0.87-1.38). Paroxetine was associated with increased heart anomalies (absolute risk 1.4% in the exposed group compared with 0.8% in women without depression; aOR 1.78, 95% CI 1.09-2.88), which decreased marginally when compared with women with diagnosed but unmedicated depression (aOR 1.67, 95% CI 1.00-2.80). CONCLUSIONS: Overall MCA risk did not increase with maternal depression or with antidepressant prescriptions. Paroxetine was associated with increases of heart anomalies, although this could represent a chance finding from a large number of comparisons undertaken.

Occurrence of fertility problems presenting to primary care: population-level estimates of clinical burden and socioeconomic inequalities across the UK.

STUDY QUESTION: What are the age-specific incident rates of clinically recorded fertility problems in women aged 15-49 years and how do they vary by socioeconomic group and geographic area. SUMMARY ANSWER: The incident rate of recorded fertility problems was highest in women age 30-34 years: about 1% of women per annum. Overall rates did not vary by socioeconomic group; however, age-specific rates varied substantially by socioeconomic deprivation quintile; among younger women, deprivation was associated with higher infertility rates. WHAT IS KNOWN ALREADY AND WHAT THIS PAPER ADDS: The rates of infertility in the UK range from 2 to 26%. Infertility definitions and denominators vary widely, and most current evidence is based on questionnaire studies that are subject to recall, reporting and selection bias. The current paper presents population-based estimates of clinically recorded fertility problems in women of reproductive age and the variation by age and socioeconomic deprivation quintile across different regions of the UK, using a nationally representative cohort of women that is larger than any previous study. Although infertility overall does not vary by socioeconomic status, consultation for fertility problems is closely related to socioeconomic patterns of women's age at first conception, demonstrating that many couples have pre-existing, rather than specifically age-related, infertility. STUDY DESIGN, SIZE, DURATION: This cohort study used data from The Health Improvement Network, a computerized primary care database of anonymized patient records from general practices across the UK, with prospective health records on over 1.7 million women between 1990 and 2010. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Our cohort included 1,776,746 women of reproductive age (age 15-49 years) who contributed one or more years of active general practice registration. We estimated rates of new clinically recorded fertility problems in these women using medical records and medications exclusively used to treat infertility. We assessed variation in age-specific incidence by socioeconomic deprivation quintile and geographic area using Poisson regression. MAIN RESULTS AND THE ROLE OF CHANCE: The rate of incident recorded fertility problems was highest in women in the 30-34 year age group (10.9 per 1000 person-years), which equates to approximately 1% of women per annum in this age group. Lowest rates were in women in the 15-19 and 45-49 year age groups (0.7 and 0.4 per 1000 person-years, respectively). Overall rates did not vary by socioeconomic group, measured using quintiles of the Townsend index. Age-specific rates, however, varied substantially with socioeconomic deprivation quintile (P-value for interaction < 0.0001) such that up to age 25, women with more deprivation had more recorded fertility problems [rate ratio (RR) comparing most to least deprived 5.6, 95% confidence interval (CI) 4.4-7.2 at 15-20 years of age]. This reversed from age 25 to 39, when women with more deprivation had fewer recorded fertility problems (RR 0.6 95% CI 0.5-0.6 at age 30-34). After age 40, there was no socioeconomic gradient in absolute rates. LIMITATIONS, REASONS FOR CAUTION: This is by far the largest population-based study to estimate clinically recorded fertility problems in women and the first in the UK to assess variation across such a broad age group from 15 to 49 years. Our data, however, did not capture women who experience difficulty in conceiving, but do not consult their general practitioner (GP) regarding fertility problems. WIDER IMPLICATIONS OF THE FINDINGS: Compared with existing estimates, our measures of the extent and distribution of recorded fertility problems in primary care are more useful for GPs, primary care trusts and policy makers for the planning and delivery of fertility services. We have shown a high burden of infertility with little geographic variation; however, the significant burden in young, more deprived women needs recognition in light of age restrictions for treatment availability for infertility in the UK. Not only does treatment access need to be universal and more equitably allocated across socioeconomic groups, but also more resources are required to reduce fertility problems by targeting modifiable risk factors. STUDY FUNDING/COMPETING INTEREST(S): There was no direct source of funding for this research work. N.N.D. completed the work as part of an M.Sc., which was funded by Developing Solutions Scholarship provided by the International Office, University of Nottingham. J.W. is supported by a University of Nottingham/National Institute for Health Research (NIHR) Senior Clinical Research Fellowship. TRIAL REGISTRATION NUMBER: Not applicable.