BackgroundHyperemesis gravidarum (HG) characterized by excessive nausea and vomiting in early pregnancy, is reported to be associated with increased risks for low birthweight (LBW), preterm birth (PTB), small-for-gestational-age (SGA) and perinatal death. Conflicting results in previous studies underline the necessity to study HG’s potential effect on pregnancy outcomes using large cohorts with valid data on exposure and outcome measures, as well as potential confounders. This study aims to investigate associations between HG and adverse pregnancy outcomes using the Norwegian Mother and Child Cohort Study (MoBa).MethodsAll singleton pregnancies in MoBa from 1998 to 2008 were included. Multivariable regression was used to estimate relative risks, approximated by odds ratios, for PTB, LBW, SGA and perinatal death. Linear regression was applied to assess differences in birthweight and gestational age for children born to women with and without HG. Potential confounders were adjusted for.ResultsAltogether, 814 out of 71,468 women (or 1.1%) had HG. In MoBa HG was not associated with PTB, LBW or SGA. Babies born to women with HG were born on average 1 day earlier than those born to women without HG; (−0.97 day (95% confidence intervals (CI): -1.80 - -0.15). There was no difference in birthweight when maternal weight gain was adjusted for; (23.42 grams (95% CI: -56.71 - 9.86). Babies born by women with HG had lower risk for having Apgar score < 7 after 1 minute (crude odds ratio was 0.64 (95% CI: 0.43 - 0.95)). No differences between the groups for Apgar score < 7 after 5 minutes were observed. Time-point for hospitalisation slightly increased differences in gestational age according to maternal HG status.ConclusionsHG was not associated with adverse pregnancy outcomes. Pregnancies complicated with HG had a slightly shorter gestational length. There was no difference in birth weight according to maternal HG-status. HG was associated with an almost 40% reduced risk for having Apgar score < 7 after 1 minute, but not after 5 minutes. The clinical importance of these statistically significant findings is, however, rather limited.

The association between use of menopausal hormone therapy (HT) and occurrence of skin malignant melanoma (SMM) is controversial. We investigated the issue in a nationwide cohort of 684,696 Norwegian women, aged 45-79 years, followed from 2004 to 2008. The study was based on linkage between Norwegian population registries. Multivariable Poisson regression models were used to estimate the effect of HT use, different HT types, routes of administration and doses of estrogen and progestin on the risk of SMM. During the median follow-up of 4.8 years, 178,307 (26%) women used HT, and 1,476 incident SMM cases were identified. Current use of HT was associated with increased risk of SMM (rate ratios (RR) = 1.19; 95% confidence interval (CI) 1.03-1.37). Plain estrogen therapy was associated with an increased risk of SMM (RR 1.45; 95% CI 1.21-1.73), both for oral (RR 1.45; 95% CI 1.09-1.93) and vaginal (RR 1.44; 95% CI 1.14-1.84) formulations, while combined estrogen and progestin therapy (EPT) was not (RR 0.91; 95% CI 0.70-1.19). We performed a dose-response analysis of estrogen and progestin in women using tablets, and found that use of estrogens was associated with increased risk (RR 1.24; 95% CI 1.00-1.53 per 1 mg/day) and use of progestins with decreased risk (RR 0.71; 95% CI 0.57-0.89 per 10 mg/month) of SMM. In conclusion, estrogens were associated with increased risk of SMM, while combinations of estrogens and progestins were not. Our results suggest that estrogens and progestins might affect the risk of SMM in opposite ways.

COVID-19 is an airway disease that also affects the nervous system. 1 Therefore, neurological and neurocognitive symptoms may be a part of the postacute sequelae of SARS-CoV-2 infection (PASC) syndrome. PASC may be found to affect a high proportion of people who had mild cases of COVID-19, and there is an urgent need for a detailed description of PASC in nonhospitalized patients. 2,3 This cohort study examines self-reported memory problems 8 months after COVID-19 infection. MethodsThis cohort study was approved by the Regional Research Ethics Committee according to the Declaration of Helsinki. Eligible participants provided informed consent by signing an online electronic consent form and completing an online baseline questionnaire and follow-up questionnaires. This study used the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.We followed a cohort of 13 001 adults who were invited after (1) having their clinical specimen analyzed for SARS-CoV-2 at 4 large accredited laboratories in Norway or (2) being randomly selected from the Norwegian population (untested). All adults who were tested for COVID between February Author affiliations and article information are listed at the end of this article.

Objective To study associations between hyperemesis gravidarum (HG) and birth outcomes.Design Population-based cohort study.Setting Norway.Sample Singleton births in the Norwegian Birth Registry, 1967-2009 (n = 2 270 363).Methods Multiple logistic regression was applied to study associations between HG and dichotomous outcomes; multiple linear regression to study associations between HG, birthweight and gestational length. Generalised estimating equations were applied to obtain valid standard errors. Sub-analysis on data with available information on smoking was conducted (1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)).Main outcome measures Small and large for gestational age (SGA/LGA), Apgar score after 5 minutes, very preterm and preterm birth (VPTB/PTB), perinatal death, stillbirth, neonatal death, birthweight and gestational length.Results No associations between HG and adverse pregnancy outcomes were observed in crude analyses, except for VPTB (odds ratio [OR] 0.79, 95% CI 0.67-0.93). In adjusted analysis, HG was associated with perinatal death (OR 1.27, 95% CI 1.08-1.48). Inverse associations were observed between HG and VPTB (OR 0.80, 95% CI 0.68-0.94) and LGA (OR 0.95, 95% CI 0.90-0.99). Sub-analyses showed no associations between HG and perinatal death (OR 1.29, 95% CI 0.91-1.83). The inverse associations between HG, VPTB and LGA were strengthened (OR 0.66, 95% CI, respectively). Exposed babies had reduced birthweight and gestational length compared with unexposed, adjusted difference À 21.4 g and À 0.5 days, respectively. Adjustment for smoking slightly strengthened the impact of HG on birthweight.Conclusions Inverse associations for HG and VPTB and LGA were observed. HG was associated with slight reductions in birthweight and gestational age.

Nested case-control designs are inevitably less efficient than full cohort designs, and it is important to use available information as efficiently as possible. Reuse of controls by inverse probability weighting may be one way to obtain efficiency improvements, and it can be particularly advantageous when two or more endpoints are analyzed in the same cohort. The controls in a nested case-control design are often matched on additional factors than at risk status, and this should be taken into account when reusing controls. Although some studies have suggested methods for handling additional matching, a thorough investigation of how this affects parameter estimates and weights is lacking. Our aim is to provide such a discussion to help developing guidelines for practitioners. We demonstrate that it is important to adjust for the matching variables in regression analyses when the matching is broken. We present three types of estimators for the inverse sampling probabilities accounting for additional matching. One of these estimators was somewhat biased when the cases and controls were matched very closely. We investigated how additional matching affected estimates of interest, with varying degree of association between the matching variables and exposure/outcome. Strong associations introduced only a small bias when the matching variables were properly adjusted for. Sometimes, exposure variables, for example, blood samples, are analyzed in batches. Rather, strong batch effects had to be present before this introduced much bias when the matching was broken. All simulations are based on a study of prostate cancer and vitamin D.

Reuse of controls in a nested case-control (NCC) study has not been considered feasible since the controls are matched to their respective cases. However, in the last decade or so, methods have been developed that break the matching and allow for analyses where the controls are no longer tied to their cases. These methods can be divided into two groups; weighted partial likelihood (WPL) methods and full maximum likelihood methods. The weights in the WPL can be estimated in different ways and four estimation procedures are discussed. In addition, we address modifications needed to accommodate left truncation. A full likelihood approach is also presented and we suggest an aggregation technique to decrease the computation time. Furthermore, we generalize calibration for case-cohort designs to NCC studies. We consider a competing risks situation and compare WPL, full likelihood and calibration through simulations and analyses on a real data example.

ObjectivesWith the present study, we aimed to investigate the association between menopausal hormone therapy (HT) and risk of colorectal cancer (CRC).SettingCohort study based on the linkage of Norwegian population-based registries.ParticipantsWe selected 466822 Norwegian women, aged 55–79, alive and residing in Norway as of 1 January 2004, and we followed them from 2004 to 2008. Each woman contributed person-years at risk as non-user, current user and/or past HT user.Outcome measuresThe outcome of interest was adenocarcinoma of the colorectal tract, overall, by anatomic site and stage at diagnosis. Incidence rate ratios (RRs) with 95% CIs were estimated by Poisson regression and were used to evaluate the association between HT and CRC incidence.ResultsDuring the median follow-up of 4.8 years, 138 655 (30%) women received HT and 3799 (0.8%) incident CRCs occurred. Current, but not past, use of HT was associated with a lower risk of CRC (RR 0.88; 95% CI 0.80 to 0.98). RRs for localised, regionally advanced and metastatic CRC were 1.13 (95% CI 0.91 to 1.41), 0.81 (95% CI 0.70 to 0.94) and 0.79 (95% CI 0.62 to 1.00), respectively. RRs for current use of oestrogen therapy (ET) were 0.91 (95% CI 0.80 to 1.04) while RR for current use of combined oestrogen–progestin therapy (EPT) was 0.85 (95% CI 0.70 to 1.03), as compared with no use of HT. The same figures for ET and EPT in oral formulations were 0.83 (95% CI 0.68 to 1.03) and 0.86 (95% CI 0.71 to 1.05), respectively.ConclusionsIn our nationwide cohort study, HT use lowered the risk of CRC, specifically the most advanced CRC.

Background: The association between use of menopausal hormone therapy and risk of cutaneous melanoma is highly debated. We investigated the issue in a Finnish nationwide cohort of women ages 50 years or older.Methods: All women who had purchased hormone therapy between 1994 and 2007 were identified from the national Medical Reimbursement Registry and linked to the Finnish Cancer Registry. We calculated standardized incidence ratios (SIR) to compare incidence of cutaneous melanoma among hormone therapy users with that of the general population.Results: During a mean follow-up of 15.6 years, 1,695 incident cutaneous melanoma cases were identified among 293,570 women who had used hormone therapy for at least 6 months. The SIRs for women who used unopposed estrogen therapy and combined estrogen-progestin therapy (EPT) for 6 to 59 months were 1.20 [95% confidence interval (CI), 1.06-1.35] and 1.00 (95% CI, 0.87-1.14; P heterogeneity ¼ 0.04). The SIRs for women who used estrogen therapy and EPT for at least 60 months were 1.37 (95% CI, 1.22-1.52) and 1.23 (95% CI, 1.13-1.34; P heterogeneity ¼ 0.15). We did not find significant differences between oral and transdermal administrations, nor between doses of estrogens.Conclusions: Use of hormone therapy, especially estrogen therapy, was associated with an increased risk of cutaneous melanoma. EPT use of less than 5 years was not associated with an increased risk of cutaneous melanoma.Impact: Our results add to the growing body of epidemiologic evidence that the use of unopposed estrogens in menopause increases the risk of cutaneous melanoma, while the addition of progestins might counteract the detrimental effect.