Multivitamin use and risk of preeclampsia: A systematic review and meta-analysis.

INTRODUCTION: Preeclampsia is associated with adverse maternal and neonatal outcomes. It is unclear whether multivitamin use reduces the risk of preeclampsia. This systematic review and meta-analysis aimed to evaluate the association between multivitamin use and the risk of preeclampsia. MATERIAL AND METHODS: We searched PubMed, Embase and the Cochrane Library from database inception to July 2021. Randomized controlled trials (RCTs), case-control and cohort studies assessing the association between multivitamin use and risk of preeclampsia were eligible. Studies of treatment with a single micronutrient were excluded. Relative risks and 95% confidence intervals (95% CI) were calculated using random-effects models. RoB2, the Newcastle Ottawa Scale and GRADE were used to assess risk of bias and quality of evidence. The protocol was registered in PROSPERO (no. CRD42021214153). RESULTS: Six studies were included (33 356 women). Only two RCTs were found, both showing a significantly decreased risk of preeclampsia in multivitamin users. These studies were not compatible for meta-analysis due to clinical heterogeneity. A meta-analysis of observational studies using a random-effects model showed an unchanged risk of preeclampsia following multivitamin use (relative risk 0.85, 95% CI 0.69-1.03). The quality of evidence according to GRADE was very low. CONCLUSIONS: Very weak evidence suggests that multivitamin use might reduce the risk of preeclampsia; however, more research is needed. Large RCTs should be prioritized. The results of this review do not allow any final conclusions to be drawn regarding a preventive effect of multivitamin use in relation to preeclampsia.

Mode of delivery and adverse short- and long-term outcomes in vertex-presenting very preterm born infants: a European population-based prospective cohort study.

OBJECTIVES: To compare mortality, morbidity and neurodevelopment by mode of delivery (MOD) for very preterm births with low prelabour risk of caesarean section (CS). METHODS: The study was a population-based prospective cohort study in 19 regions in 11 European countries. Multivariable mixed effects models and weighted propensity score models were used to estimate adjusted odds ratios (aOR) by observed MOD and the unit's policy regarding MOD. Population: Singleton vertex-presenting live births at 24 + 0 to 31 + 6 weeks of gestation without serious congenital anomalies, preeclampsia, HELLP or eclampsia, antenatal detection of growth restriction and prelabour CS for fetal or maternal indications. RESULTS: Main outcome measures: A composite of in-hospital mortality and intraventricular haemorrhage (grade III/IV) or periventricular leukomalacia. Secondary outcomes were components of the primary outcome, 5 min Apgar score <7 and moderate to severe neurodevelopmental impairment at two years of corrected age. The rate of CS was 29.6% but varied greatly between countries (8.0-52.6%). MOD was not associated with the primary outcome (aOR for CS 0.99; 95% confidence interval [CI] 0.65-1.50) when comparing units with a systematic policy of CS or no policy of MOD to units with a policy of vaginal delivery (aOR 0.88; 95% CI 0.59-1.32). No association was observed for two-year neurodevelopment impairment for CS (aOR 1.15; 95% CI 0.66-2.01) or unit policies (aOR 1.04; 95% CI 0.63-1.70). CONCLUSIONS: Among singleton vertex-presenting live births without medical complications requiring a CS at 24 + 0 to 31 + 6 weeks of gestation, CS was not associated with improved neonatal or long-term outcomes.

[Magnesium sulphate treatment decreases the risk of cerebral palsy after preterm birth].

Children born preterm have an increased risk of severe morbidity, e.g. cerebral palsy (CP), compared to children born at term. CP cannot be treated, which is why a prophylactic approach is essential, as argued in this review. Six randomised controlled trials (RCTs) have provided data on MgSO4 treatment as CP neuroprotection in preterm birth, including a new RCT from Denmark. Recently, an updated meta-analysis with trial sequential analysis detected a significant neuroprotective effect of MgSO4 treatment in preterm birth. There is now sufficient evidence, that MgSO4 treatment should be used as neuroprotection in preterm birth.

Multivitamin intake does not affect the risk of preterm and very preterm birth.

INTRODUCTION: The aim of this study was to assess the association between multivitamin intake during pregnancy and the risk of preterm birth and very preterm birth. METHODS: The study population comprised 15,629 women from the Copenhagen Pregnancy Cohort with data on pregnancy multivitamin intake during their first trimester who gave birth to singletons from October 2012 to October 2016. Data on pregnancy multivitamin intake were linked to the Medical Birth Registry to identify the birth outcome. The main outcome measures were preterm birth before 37 weeks of gestation and very preterm birth before 32 weeks of gestation. RESULTS: Among the included women, 85.6% had taken daily pregnancy multivitamins during their first trimester. We found no evidence that pregnancy multivitamin intake during the first trimester was associated with a decreased risk of preterm birth (adjusted odds ratio (OR) = 1.01; 95% confidence interval (CI): 0.77-1.33) or very preterm birth (adjusted OR = 1.06; 95% CI: 0.63-1.77). Stratification for BMI into lesser-than 25 kg/m2 and ≥ 25 kg/m2 did not alter these findings. CONCLUSIONS: Pregnancy multivitamin intake during the first trimester was not associated with a decreased risk of preterm birth or very preterm birth among women in a high-income population. FUNDING: none. TRIAL REGISTRATION: not relevant.

Multivitamin use and risk of preeclampsia in a high-income population: A cohort study.

OBJECTIVE: The objective of this study was to examine the association between multivitamin use in the periconceptional period and the risk of preeclampsia. STUDY DESIGN: The association was investigated in a prospective cohort study. 15,154 deliveries in women followed at a large university hospital in Denmark were included between 16 September 2012 and 31 October 2016. Pregnant women were sent a questionnaire containing items related to socio-demographic-, lifestyle- and health factors. The responses on multivitamin use were merged with the preeclampsia diagnosis from the Danish Medical Birth Registry. We used multiple logistic regression analyses to assess the association and to adjust for potential confounders. MAIN OUTCOME MEASURES: The outcome of interest, preeclampsia, included the preeclampsia subtypes eclampsia and HELLP (Haemolysis, Elevated Liver enzymes, and Low Platelets) syndrome. RESULTS: In total 12,954 women (85%) reported multivitamin use. A diagnosis of preeclampsia was found in 397 women (2.6%). We found a similar risk of preeclampsia in multivitamin user and non-users, adjusted odds ratio (AOR) for periconceptional multivitamin use = 0.97 (95% CI: 0.70 to 1.36) and AOR for early pregnancy multivitamin use = 0.97 (95% CI: 0.71 to 1.32). Subgroup analyses stratified on body mass index showed that among women with overweight, both periconceptional and early pregnancy multivitamin use were associated with a statistically significant lower risk of preeclampsia (AOR = 0.49, 95% CI: 0.24 to 0.99 and AOR = 0.35, 95% CI: 0.18 to 0.69, respectively). CONCLUSION: Periconceptional- and early pregnancy multivitamin use was found to be associated with a similar risk of preeclampsia compared to non-users.

Alcohol Intake in Early Pregnancy and Spontaneous Preterm Birth: A Cohort Study.

BACKGROUND: Limited research has addressed whether maternal alcohol intake in early pregnancy increases the risk of spontaneous preterm birth. In the current study, we examined how alcohol binge drinking and weekly alcohol intake in early pregnancy were associated with spontaneous preterm birth in a contemporary cohort of Danish women. METHODS: We included 15,776 pregnancies of 14,894 women referred to antenatal care at Copenhagen University Hospital, Denmark, between 2012 and 2016. Self-reported alcohol intake in early pregnancy was obtained from a Web-based questionnaire completed prior to the women's first visit at the department. Information on spontaneous preterm birth was extracted from the Danish Medical Birth Register. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) of spontaneous preterm birth according to self-reported alcohol binge drinking and weekly intake of alcohol in early pregnancy were derived from Cox regression. RESULTS: Women reporting 1, 2, and ≥ 3 binge drinking episodes had an aHR for spontaneous preterm birth of 0.88 (95% CI 0.68 to 1.14), 1.34 (95% CI 0.98 to 1.82), and 0.93 (95% CI 0.62 to 1.41), respectively, compared to women with no binge drinking episodes. Women who reported an intake of ≥ 1 drink per week on average had an aHR for spontaneous preterm birth of 1.09 (95% CI 0.63 to 1.89) compared to abstainers. When restricting to nulliparous women or cohabiting women with ≥ 3 years of higher education, this estimate was 1.28 (95% CI 0.69 to 2.40) and 1.20 (95% CI 0.67 to 2.15), respectively. CONCLUSION: We found no evidence that maternal alcohol intake in early pregnancy was associated with a higher risk of spontaneous preterm birth, neither for alcohol binge drinking nor for a low average weekly intake of alcohol.

Characteristics of first-trimester screening of non-responders in a high-uptake population.

INTRODUCTION: Our aim was to compare demographic, social and reproductive health-related medical factors between women who did and women who did not undergo combined first-trimester screening (cFTS) and to examine their reasons for declining a screening offer, especially whether non-participation was an informed choice. METHODS: This was a nationwide survey conducted in Denmark in 2014. A structured questionnaire with 33 questions relating to demographical data and medical history was mailed to 1,495 randomly selected women who gave birth in 2012. Half of the women were selected among the population without cFTS, the other half from those with cFTS. A cohort of 20 women tested the questionnaire for consistency. The results are based on the responders (58%). RESULTS: The response rate was 88% among the women with cFTS and 19% among the women without. Not having a cFTS performed was associated with the following factors: country of origin other than Denmark (p < 0.01), less education (p < 0.01) and unemployment (p < 0.01). These women more often had a religious belief (p < 0.01), and had undergone fewer induced abortions (p = 0.01). They felt less informed about the cFTS (p < 0.01) and thought it was a more difficult decision (p < 0.01) than the women who had undergone cFTS. The main reason for declining cFTS was a wish to keep the child regardless of any cFTS results (82%). CONCLUSIONS: Women without cFTS differ from those who undergo cFTS. Not undergoing cFTS seemed most often to be the result of a conscious choice based on ethical considerations, rather than being the result of a lack of information. However, a low response rate decreases the strength of our conclusions. FUNDING: none. TRIAL REGISTRATION: not relevant.

[Evidence exists for prophylactic magnesium sulphate as a neuroprotector in premature births]. / Der er evidens for profylaktisk magnesiumsulfat som neuroprotektion ved præmature fødsler.

Preterm birth increases the child's risk of cerebral palsy. Observational studies as well as randomized studies find that magnesium sulphate given to women in preterm birth decreases such risk. A Cochrane meta-analysis of the randomized studies shows no change in mortality, whereas some observational studies find a mortality decrease. It is important to identify the neuroprotective mechanism and to decide whether these results are relevant in the current Danish obstetrical practice. Should we use magnesium sulphate now or should questions about doses, time of administration and maternal side effects be answered first?

[Photo-onycholysis observed in connection with doxycycline for malaria prophylaxis]. / Fotoonykolyse ses ved brug af doxycyklin som malariaprofylakse.

We present two cases of phototoxic onycholysis secondary to doxycycline treatment as malaria prophylaxis. Onycholysis is a rare side-effect to treatment with doxycycline and other tetracyclines. Some physicians are unaware of this risk. Due to the increasing travel activity to malaria endemic regions, it is important to be aware of the side effects - including onycholysis - following the use of tetracyclines and it is essential to inform the patients of such effects. Spontaneous recovery follows within a few months after discontinuing the drug and there is no need for further treatment.