Hedvig Nordeng

Prenatal paracetamol exposure and child neurodevelopment: a sibling-controlled cohort study

BACKGROUND Paracetamol is used extensively during pregnancy, but studies regarding the potential neurodevelopmental sequelae of foetal paracetamol exposure are lacking. Method Between 1999 and 2008 all pregnant Norwegian women were eligible for recruitment into the prospective Norwegian Mother and Child Cohort Study. The mothers were asked to report on their use of paracetamol at gestational weeks 17 and 30 and at 6 months postpartum. We used data on 48 631 children whose mothers returned the 3-year follow-up questionnaire by May 2011. Within this sample were 2919 same-sex sibling pairs who were used to adjust for familial and genetic factors. We modelled psychomotor development (communication, fine and gross motor development), externalizing and internalizing behaviour problems, and temperament (emotionality, activity, sociability and shyness) based on prenatal paracetamol exposure using generalized linear regression, adjusting for a number of factors, including febrile illness, infections and co-medication use during pregnancy. RESULTS The sibling-control analysis revealed that children exposed to prenatal paracetamol for more than 28 days had poorer gross motor development [β 0.24, 95% confidence interval (CI) 0.12-0.51], communication (β 0.20, 95% CI 0.01-0.39), externalizing behaviour (β 0.28, 95% CI 0.15-0.42), internalizing behaviour (β 0.14, 95% CI 0.01-0.28), and higher activity levels (β 0.24, 95% CI 0.11-0.38). Children exposed prenatally to short-term use of paracetamol (1-27 days) also had poorer gross motor outcomes (β 0.10, 95% CI 0.02-0.19), but the effects were smaller than with long-term use. Ibuprofen exposure was not associated with neurodevelopmental outcomes. CONCLUSION Children exposed to long-term use of paracetamol during pregnancy had substantially adverse developmental outcomes at 3 years of age.

Medication use in pregnancy: a cross-sectional, multinational web-based study

Objectives Intercountry comparability between studies on medication use in pregnancy is difficult due to dissimilarities in study design and methodology. This study aimed to examine patterns and factors associated with medications use in pregnancy from a multinational perspective, with emphasis on type of medication utilised and indication for use. Design Cross-sectional, web-based study performed within the period from 1 October 2011 to 29 February 2012. Uniform collection of drug utilisation data was performed via an anonymous online questionnaire. Setting Multinational study in Europe (Western, Northern and Eastern), North and South America and Australia. Participants Pregnant women and new mothers with children less than 1 year of age. Primary and secondary outcome measures Prevalence of and factors associated with medication use for acute/short-term illnesses, chronic/long-term disorders and over-the-counter (OTC) medication use. Results The study population included 9459 women, of which 81.2% reported use of at least one medication (prescribed or OTC) during pregnancy. Overall, OTC medication use occurred in 66.9% of the pregnancies, whereas 68.4% and 17% of women reported use of at least one medication for treatment of acute/short-term illnesses and chronic/long-term disorders, respectively. The extent of self-reported medicated illnesses and types of medication used by indication varied across regions, especially in relation to urinary tract infections, depression or OTC nasal sprays. Women with higher age or lower educational level, housewives or women with an unplanned pregnancy were those most often reporting use of medication for chronic/long-term disorders. Immigrant women in Western (adjusted OR (aOR): 0.55, 95% CI 0.34 to 0.87) and Northern Europe (aOR: 0.50, 95% CI 0.31 to 0.83) were less likely to report use of medication for chronic/long-term disorders during pregnancy than non-immigrants. Conclusions In this study, the majority of women in Europe, North America, South America and Australia used at least one medication during pregnancy. There was a substantial inter-region variability in the types of medication used.

Pregnancy outcome after exposure to antidepressants and the role of maternal depression: results from the Norwegian Mother and Child Cohort Study.

Abstract Results of previous studies on the safety of antidepressants during pregnancy have been conflicting. The primary objective of this study was to investigate whether first-trimester exposure to antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs), was associated with increased risk of congenital malformations. The secondary objective was to examine the effects of exposure to antidepressants during pregnancy on birth weight and gestational age. We included 63,395 women from the Norwegian Mother and Child Cohort Study. The women had completed 2 self-administered questionnaires at gestational weeks 17 and 30 on medication use and medical, sociodemographic, and psychological factors. Data on pregnancy outcome were retrieved from the Medical Birth Registry of Norway. Of the 63,395 women, 699 (1.1%) reported using antidepressants during pregnancy, most frequently SSRIs (0.9%). Exposure to SSRIs during the first trimester was not associated with increased risk of congenital malformations in general (adjusted odds ratio [OR], 1.22; 95% confidence interval [CI], 0.81–1.84) or cardiovascular malformations (adjusted OR, 1.51; 95% CI, 0.67–3.43). Exposure to antidepressants during pregnancy was not associated with increased risk of preterm birth (adjusted OR, 1.21; 95% CI, 0.87–1.69) or low birth weight (adjusted OR, 0.62; 95% CI, 0.33–1.16). This study does not suggest a strongly increased risk of malformations, preterm birth, or low birth weight following prenatal exposure to antidepressants. Without adjustments for level of maternal depression and various sociodemographic and lifestyle factors, antidepressant use during pregnancy would wrongly have been associated with an increased risk of preterm birth.

Impact of socio‐demographic factors, knowledge and attitude on the use of herbal drugs in pregnancy

Background.  Herbal drugs are often promoted as ‘natural’ and ‘safe’. These claims may especially attract pregnant women who are often concerned about their unborn childs well‐being. Few studies have assessed the use of herbal drugs in pregnancy and the factors related to this use.

Treatment with selective serotonin reuptake inhibitors in the third trimester of pregnancy: effects on the infant

Pharmacotherapy in pregnant women is often necessary to treat chronic or relapsing depression or anxiety disorders. Studies that have evaluated the safety of selective serotonin reuptake inhibitors (SSRIs) in early pregnancy have not shown an enhanced risk of major congenital malformations and these results may have contributed to the increasing use of these agents during pregnancy. Fewer studies have assessed the safety of SSRIs in the third trimester of pregnancy. This article reviews available human data on the safety of SSRI treatment in the third trimester. The main purpose is to present and discuss the existing literature on the risks to the infant and to suggest treatment guidelines for the use of SSRIs in late pregnancy. The use of SSRIs in the third trimester has shown various perinatal complications, most frequently respiratory distress, irritability and feeding problems. Further studies are needed to evaluate the frequency of these complications and to elucidate whether the symptoms represent a direct serotonergic effect or are a drug withdrawal effect. Studies have shown conflicting results with respect to whether SSRI exposure decreases birthweight and increases the risk of premature delivery. A few case reports have described intracerebral haemorrhage in neonates after maternal SSRI treatment, but it is not known whether the frequency of such complications is higher than in unexposed neonates. Data on possible long-term effects of prenatal SSRI exposure on psychomotor and behavioural development are very sparse. Our interpretation of the current literature suggests that the risk of not receiving adequate antidepressant treatment in the third trimester when indicated outweighs the risks of adverse events in the infant. Thus, adequate pharmacological treatment should not be withheld from a depressed pregnant woman in late pregnancy. However, the neonate should be monitored for possible adverse effects after maternal use of an SSRI in the third trimester.

Antidepressant use during pregnancy: the benefit-risk ratio

Antidepressants are used commonly in pregnancy. Physicians who provide health care for pregnant women with depression must balance maternal well-being with potential fetal risks of these medications. Over the last decade, scores of original and review articles have discussed whether selective serotonin reuptake inhibitors-selective serotonin norepinephrine reuptake inhibitors possess risks to the fetus; however, very little has been done to integrate these potential risks, if they exist, into an overall context of a benefit:risk ratio. This review aims at presenting an updated analysis of fetal and maternal exposure to selective serotonin or norepinephrine reuptake inhibitors to allow an evidence-based benefit:risk ratio. When a psychiatric condition necessitates pharmacotherapy, the benefits of such therapy far outweigh the potential minimal risks of cardiac malformations, primary pulmonary hypertension of the newborn infant, or poor neonatal adaptation syndrome.

Characteristics of women who continue smoking during pregnancy: a cross-sectional study of pregnant women and new mothers in 15 European countries

BackgroundSome women continue smoking during pregnancy despite the extensive information available on the dangers smoking poses to their fetus. This study aimed to examine the prevalence and determinants of smoking before and during pregnancy and the extent of smoking during pregnancy from a European perspective in relation to maternal sociodemographic characteristics, health literacy, morbidity, and pregnancy-related factors.MethodsThis multinational, web-based study evaluated pregnant women and new mothers in 15 European countries recruited from October 2011 to February 2012. Data were collected via an anonymous online questionnaire.ResultsOf 8344 women included, 2944 (35.3%) reported smoking before pregnancy, and 771 (26.2%) continued smoking during pregnancy, 88 (11.4%) of whom smoked more than 10 cigarettes per day. There was a wide variation among the 15 European countries in smoking rates before and during pregnancy, ranging from 25.0% (Sweden) to 50.0% (Croatia) before and 4.2% (Iceland) to 18.9% (Croatia) during pregnancy. Women who lived in Eastern Europe, without a spouse/partner, with a low education level and unplanned pregnancy, who did not take folic acid, and consumed alcohol during pregnancy were the most likely to smoke before pregnancy. Women who lived in Eastern or Western Europe, without a spouse/partner, with a low education level and health literacy, being a housewife, having previous children and unplanned pregnancy, and who did not take folic acid were the most likely to continue smoking during pregnancy. Women who smoked more than 10 cigarettes per day during pregnancy were the most likely to be living in Eastern Europe and to have a low education level.ConclusionWomen with fewer resources living in Western or Eastern Europe are more likely not only to smoke before pregnancy but also to continue smoking during pregnancy. These high-risk women are characterized as living alone, having high school or less as highest education level, having low health literacy, being a housewife, having previous children, having unplanned pregnancy, and no use of folic acid. Our findings indicated that focus on smoking cessation is important in antenatal care in Europe as many women smoke before pregnancy, and still continue to do so in pregnancy.

Triptan exposure during pregnancy and the risk of major congenital malformations and adverse pregnancy outcomes: results from the Norwegian Mother and Child Cohort Study.

(Headache 2010;50:563‐575)

Herbal medicine use in pregnancy: results of a multinational study

BackgroundThe use of complementary and alternative medicines (CAM) is growing in the general population. Herbal medicines are used in all countries of the world and are included in the top CAM therapies used.MethodsA multinational study on how women treat disease and pregnancy-related health ailments was conducted between October 2011 and February 2012 in Europe, North and South America and Australia. In this study, the primary aim was to determine the prevalence of herbal medicine use in pregnancy and factors related to such use across participating countries and regions. The secondary aim was to investigate who recommended the use of herbal medication in pregnancy.ResultsThere were 9,459 women from 23 countries participating in the study. Of these, 28.9% reported the use of herbal medicines in pregnancy. Most herbal medicines were used for pregnancy-related health ailments such as cold and nausea. Ginger, cranberry, valerian and raspberry were the most commonly used herbs in pregnancy. The highest reported rate of herbal use medicines was in Russia (69%). Women from Eastern Europe (51.8%) and Australia (43.8%) were twice as likely to use an herbal medicine versus other regions. Women using herbal medicines were characteristically having their first child, non-smokers, using folic acid and consuming some alcohol in pregnancy. Also, women who were currently students and women with an education other than a high school degree were more likely to use herbal medicines than other women. Although 1 out of 5 women stated that a physician had recommended the herbal use, most women used herbal medicine in pregnancy on their own initiative.ConclusionsIn this multinational study herbal medicine use in pregnancy was high although there were distinct differences in the herbs and users of herbal medicines across regions. Most commonly the women self-medicated with herbal medicine to treat pregnancy-related health ailments. More knowledge regarding the efficacy and safety of herbal medicines in pregnancy is warranted.

Use of herbal drugs during pregnancy among 600 Norwegian women in relation to concurrent use of conventional drugs and pregnancy outcome

PURPOSE The purpose of this study was to investigate the use of herbal drugs by pregnant women in relation to concurrent use of conventional drugs, delivery, and pregnancy outcome. METHOD 600 women at Stavanger University Hospital Norway were interviewed using a structured questionnaire within five days after delivery. Medical birth charts were reviewed with respect to pregnancy outcome. RESULTS In all, 39.7% of the women reported having used herbal drugs during pregnancy, most commonly ginger, iron-rich herbs, echinacea and cranberry. Although 86.3% of the women reported having used conventional drugs during pregnancy there were few potential interactions between herbal drugs and conventional drugs. There was a significant association between the use of iron-rich herbs during pregnancy and high birthweight, and use of raspberry leaves and caesarean delivery. CONCLUSION Use of herbal drugs is common during pregnancy and indicates a need for documentation about their safety in pregnancy.