Reproductive history of parous women and urinary incontinence in midlife: A National Birth Cohort follow-up study.

OBJECTIVE: To investigate how reproductive history was associated with urinary incontinence in midlife. DESIGN: A follow-up study. SETTING: Denmark. POPULATION: A total of 39 977 mothers who participated in the Maternal Follow up (2013-2014) in the Danish National Birth Cohort. National registries provided their reproductive history. METHODS: How parity, mode of birth and obstetric tears associated with urinary incontinence were estimated with adjusted odds ratios (OR) and 95% CI using logistic regression. MAIN OUTCOME MEASURES: Self-reported urinary incontinence including subtypes stress, urge and mixed urinary incontinence. RESULTS: At an average age of 44 years, the prevalence of any urinary incontinence was 32% (21% stress, 2% urge, and 8% mixed urinary incontinence). Women with two births more often had urinary incontinence than women with one birth (OR 1.20, 95% CI 1.10-1.31). Compared with women with only spontaneous births, a history of only caesarean sections was associated with much lower odds of urinary incontinence (OR 0.39, 95% CI 0.35-0.42) and a history of instrumental births with slightly lower odds (OR 0.92, 95% CI 0.86-0.98). Compared with no tear/first-degree tear as the largest tear, episiotomy was associated with less urinary incontinence (OR 0.91, 95% CI 0.86-0.97) whereas third/fourth-degree tears were associated with more (OR 1.14, 95% CI 1.04-1.25). Findings were mainly explained by similar associations with stress and mixed urinary incontinence. CONCLUSIONS: Vaginal birth was associated with a higher risk of long-term urinary incontinence, but our results indicate that this risk may be reduced by shortening the second stage of birth.

Urinary Incontinence in Midlife According to Weight Changes Across and After Childbearing Years.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate how weight change across and after the childbearing years was associated with urinary incontinence (UI) in midlife. METHODS: Data were obtained from 35,645 women responding to the Maternal Follow-up questionnaire in the Danish National Birth Cohort in 2013-2014. Outcome was self-reported UI and its subtypes. Exposures were changes in body mass index (BMI) across and after the childbearing years. Adjusted odds ratios were estimated using logistic regression. RESULTS: At follow-up, the mean age was 44 years and 32% experienced UI. Compared with stable weight, weight gain across the childbearing years of > 1 to 3, > 3 to 5 or > 5 BMI units increased the odds of any UI by 15%, 27%, and 41% respectively. For mixed UI, the odds increased by 23%, 41%, and 68% in these groups. Weight gain after childbearing showed the same pattern, but with a higher increase in the odds of mixed UI (25%, 60%, and 95% in the respective groups). Women with any weight loss during this period had 9% lower odds of any UI than women with a stable weight. CONCLUSIONS: Weight gain across and after childbearing increased the risk of UI in midlife, especially the subtype mixed UI. Weight loss after childbearing decreased the risk.

Body mass index, waist circumference, and urinary incontinence in midlife: A follow-up of mothers in the Danish National Birth Cohort.

BACKGROUND: Obesity is a modifiable risk factor for urinary incontinence, yet few studies have investigated how waist circumference as compared to body mass index (BMI) influences the risk of urinary incontinence. OBJECTIVE: To estimate how BMI and waist circumference associates with risk of urinary incontinence in midlife and determine which of the two is the strongest predictor of urinary incontinence. METHODS: Cohort study among mothers in the Danish National Birth Cohort. Weight and waist circumference were self-reported 7 years after cohort entry. Symptoms of urinary incontinence in midlife were self-reported using the International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) and analyzed continuously and as presence or absence of any, stress (SUI), urgency (UUI), and mixed (MUI) urinary incontinence. Linear and log binomial regressions were used to calculate mean differences and risk ratios (RR) with 95% confidence intervals (CI). Restricted cubic splines were generated to explore nonlinear relationships. RESULTS: Among 27 254 women at a mean age of 44.2 years, any urinary incontinence was reported by 32.1%, SUI by 20.9%, UUI by 2.4%, and MUI by 8.6%. For all outcomes, increases in risk were similar with higher BMI and waist circumference. The estimates of association were strongest for MUI (RR 1.10, 95% CI 1.08;1.12 and RR 1.12, 95% CI 1.10;1.14 for half a standard deviation increase in BMI and waist circumference, respectively). While increases in risk of the other outcomes were seen across the entire range of BMI and waist circumference, the risk of SUI rose until BMI 28 kg/m2 (waist circumference 95 cm), and then fell slightly. CONCLUSIONS: Symptoms of urinary incontinence and prevalence of any urinary incontinence, SUI, UUI, and MUI increased with higher BMI and waist circumference. Self-reported BMI and waist circumference were equally predictive of urinary incontinence.

Mode of birth and long-term maternal mental health: A follow-up study in the Danish National Birth Cohort.

BACKGROUND: Cesarean birth has been associated with increased risks of short-term mental health problems. Little is known about whether these associations persist in the long term. This study aimed to estimate the associations between mode of birth and maternal mental health in midlife while considering mental health before and during pregnancy. METHODS: Cohort study among mothers in the Danish National Birth Cohort. Birth mode for each woman's entire reproductive history was obtained from Danish national registries. Symptoms of depression and stress in midlife were self-reported using validated scales. Log binomial regression was used to calculate risk ratios (RR) with 95% confidence intervals (CI) for the association between birth mode and depressive symptoms. Linear regression was used to calculate mean difference in stress score by birth mode. RESULTS: Among 42,872 women, 15.5% reported depressive symptoms at follow-up, where they were, on average, 43.9 years and 11.2 years after their last birth. Compared with women who only ever had spontaneous vaginal births, women who only had cesarean births, or had both cesarean and vaginal births with the last birth by cesarean, reported slightly more symptoms of depression (RR 1.10, 95% CI 1.01;1.20) and stress (mean difference 0.68 on a 100-point scale, 95% CI 0.10;1.26). CONCLUSION: Whether due to the birth experience or underlying factors, depression and stress in midlife were more frequent in women with only cesarean births or whose last birth was by cesarean compared with women with vaginal births.

Maternal Medication Use and Childhood Cancer in Offspring-Systematic Review and Considerations for Researchers.

Cancer is an important cause of childhood mortality, yet the etiology is largely unknown. A combination of pre- and postnatal factors is thought to be implicated, including maternal medication use. We aimed to provide: 1) a systematic review of peer-reviewed publications on associations between maternal medication use and childhood cancer, with a focus on study design and methodology; and 2) suggestions for how to increase transparency, limit potential biases, and improve comparability in studies on maternal medication use and childhood cancer. We conducted a systematic search in the PubMed, Embase, Scopus, Cochrane, and Web of Science databases to June 8, 2020. Altogether, 112 studies were identified. The reviewed studies were heterogeneous in study design, exposure, and outcome classification. In 21 studies (19%), the outcome was any childhood cancer. Of the 91 papers that reported on specific types of cancer, 62% did not report the cancer classification system. The most frequently investigated medication groups were sex hormones (46 studies, excluding fertility medications), and antiinfectives (37 studies). Suggestions for strengthening future pharmacoepidemiologic studies on maternal medication use and childhood cancer relate to choice of cancer classification system, exposure windows, and methods for identification of, and control for, potential confounders.

Prenatal exposure to non-steroidal anti-inflammatory drugs and risk of attention-deficit/hyperactivity disorder: A follow-up study in the Norwegian mother, father and child cohort.

PURPOSE: To estimate the association between Attention-Deficit/Hyperactivity Disorder (ADHD) in children in preschool and primary school, and prenatal exposure to non-steroidal anti-inflammatory drugs (NSAIDs) by timing and duration. METHODS: This study was based on the Norwegian Mother, Father and Child Cohort Study linked to the Medical Birth Registry of Norway, the Norwegian Patient Registry (NPR) and the Norwegian Prescription Database (NorPD). NSAID exposure was identified by maternal self-report in pregnancy. Child diagnosis of ADHD was obtained from NPR and NorPD. Symptoms of ADHD at age 5 years were measured using Conners' Parent Rating Scale-Revised, where higher scores correspond to more symptoms. To account for time-varying exposure and confounders, marginal structural models were fitted to estimate hazard ratios and mean difference in z-scores. RESULTS: The analyses on ADHD diagnosis and ADHD symptoms included 56 340 and 34 961 children respectively. Children exposed to NSAIDs prenatally had no increased risk of ADHD diagnosis (first trimester: HR 1.12, 95% CI 0.86;1.45, second trimester: HR 0.98, 95% CI 0.69;1.38, third trimester: HR 0.68, 95% CI 0.31; 1.46) or ADHD symptoms (first trimester: standardized mean difference 0.03, 95% CI -0.03;0.09, second trimester: standardized mean difference 0.03, 95% CI -0.04;0.11, third trimester: standardized mean difference 0.11, 95% CI -0.03; 0.25). There was no duration-response relationship for either outcome. CONCLUSION: Though non-differential misclassification of the exposure may have attenuated results, these findings are reassuring and suggest no substantially increased risk of ADHD diagnosis or symptoms in children prenatally exposed to NSAIDs, regardless of timing or duration.

Menstrual pain and sexual health in mothers-A cross-sectional study in the Danish National Birth Cohort.

INTRODUCTION: Prevalence and consequences of menstrual pain have mainly been studied in younger women. We aimed to describe the prevalence of menstrual pain in mothers and its association with sexual problems. MATERIAL AND METHODS: A cross-sectional study using questionnaire data from the Maternal Follow Up (2013-2014) in the Danish National Birth Cohort (1996-2002). Of 82 569 eligible mothers, 43 639 (53%) completed the follow up. Of these, 24 000 women had a partner, and answered the questions on menstrual pain. Log binomial regression was used to calculate prevalence proportion ratios (PPR) with 95% CI for the association between menstrual pain and specific sexual problems. RESULTS: Menstrual pain was reported by 16 464 women (69%), and severe menstrual pain by 19%. Treatment had previously been requested by 19% of women with menstrual pain. The most common treatment was oral contraceptives, but for 18% of women seeking treatment, no treatment was given. Women with menstrual pain were more likely to report reduced sexual desire (PPR 1.22, 95% CI 1.15-1.29), vaginismus (PPR 1.31, 95% CI 0.96-1.78), and dyspareunia (PPR 1.63, 95% CI 1.47-1.81), in particular deep dyspareunia (PPR 1.92, 95% CI 1.67-2.20). CONCLUSIONS: A majority of Danish mothers in mid-life experienced menstrual pain, and these women more often reported reduced sexual desire, vaginismus, and deep dyspareunia. Few women sought and received treatment for menstrual pain. Healthcare practitioners should be aware that menstrual pain can affect parous women and co-occurs with sexual problems. Future studies should identify barriers to seeking and receiving adequate treatment for menstrual pain.

Fertility treatment and oral contraceptive discontinuation for identification of pregnancy planning in routinely collected health data - an application to analgesic and antibiotic utilisation.

BACKGROUND: Women with unplanned pregnancies use folic acid less frequently, and more often use potentially teratogenic medications in the first trimester. Yet most studies based on routinely collected data lack information on pregnancy planning. Further, only pregnancies proceeding beyond a certain gestational age appear in routinely collected data, creating the possibility for collider-stratification bias. If pregnancy intention could be identified, pregnancies could be ascertained earlier. This study aimed to investigate fertility treatment and discontinuation of oral contraception (OC) as proxies for pregnancy planning by describing variations in patterns of prescription fills for antibiotics and analgesics during the peri-pregnancy period by these proxies of pregnancy intention. METHODS: Fertility treatment with clomiphene and discontinuation of OC were identified in the Norwegian Prescription Database (NorPD) and linked with data from the Medical Birth Registry of Norway for the years 2006 to 2017. Filled prescriptions for antibiotics and analgesics from NorPD were displayed for women on fertility treatment, women who discontinued OC before pregnancy, and women who discontinued during pregnancy. RESULTS: Of 172,585 included pregnancies, fertility treatment was identified in 19,449, and OC discontinuation before or during pregnancy in 153,136. Women who discontinued OC during pregnancy were less likely to use preconception folic acid (25.4%) than women who discontinued before pregnancy (32.9%), and women on fertility treatment (51.0%). Proportions of first trimester prescription fills were 4.9% (analgesics) and 12.8% (antibiotics) for women who discontinued OC during pregnancy, compared to 4.0 and 11.4% in women who discontinued OC before pregnancy, and 4.7 and 11.0% in women on fertility treatment. CONCLUSIONS: There were no substantial differences in patterns of prescription fills for analgesics and antibiotics before or during pregnancy by fertility treatment and OC discontinuation. This suggests that there were few differences in medication use between women with planned and unplanned pregnancies, or that fertility treatment and timing of OC discontinuation from routinely collected health data cannot stand alone in the identification of unplanned pregnancies. A narrower definition of OC discontinuation during pregnancy seemed to be a better proxy, but this should be confirmed in other studies.

The effect of Xylocaine spray on suture material degradation.

OBJECTIVES: To compare the tensile strength of fast absorbable Polyglactin 910 suture material when impregnated with various agents for local anesthesia and to investigate whether the presence of ethanol in Xylocaine spray could explain a potential reduction in tensile strength after use of Xylocaine spray. METHODS: In all, 120 suture samples of Polyglactin 910 were divided into four groups of 30. These four groups were randomly impregnated with isotonic sodium chloride, isotonic sodium chloride plus Xylocaine spray, isotonic sodium chloride plus Xylocaine gel, or isotonic sodium chloride plus ethanol. After impregnation, the sutures were stored in sealed glass tubes in a heating cabinet at 37°C for 72 h. Thereafter, the tensile strength of these 120 samples was assessed by a universal tensile testing machine. The maximal force needed to break the suture material was recorded in newtons (N). RESULTS: Fast absorbable Polyglactin 910 suture material impregnated with Xylocaine spray or ethanol showed weakened tensile strength (mean values 11.40 and 11.86 N, respectively), whereas the specimens impregnated with Xylocaine gel or sodium chloride retained their tensile strength better (mean values 13.81 and 13.28 N, respectively; mean difference between Xylocaine gel and Xylocaine spray -2.41 N, P < 0.001). CONCLUSION: In this in vitro experiment, ethanol and Xylocaine spray weakened the tensile strength of fast absorbable Polyglactin 910 sutures. Use of Xylocaine spray, which contains ethanol, for local anesthesia might lead to early breakdown of the suture material and wound rupture. The authors suggest caution when using Xylocaine spray in combination with fast absorbable Polyglactin 910 suture.

Mode of delivery and short-term maternal mental health: A follow-up study in the Danish National Birth Cohort.

OBJECTIVE: To estimate associations between mode of delivery and maternal mental health 6 months postpartum. METHODS: Follow-up of mothers in the Danish National Birth Cohort. Symptoms of anxiety, depression or stress were self-reported at gestational week 30 and 6 months postpartum. Mode of delivery was categorized as spontaneous vaginal birth, instrumental vaginal birth, planned cesarean section and emergency cesarean section. Multiple linear and logistic regression models were used to compute differences and odds ratios (ORs) with 95% confidence intervals (CIs) for associations between delivery mode and mental health indicators adjusted for mental health before and during pregnancy. RESULTS: Among 54 474 mothers, mental health indicators improved from pregnancy to 6 months postpartum for all delivery modes. Improvement was smallest in mothers with emergency cesarean section. Thus, compared to women with a spontaneous vaginal birth, women with emergency cesarean section more frequently reported symptoms of anxiety (OR 1.11; 0.98-1.24), depression (OR 1.25; 1.09-1.43) and stress (OR 1.14; 1.01-1.29) 6 months postpartum, and women with planned cesarean section more frequently reported symptoms of anxiety (OR 1.15; 1.01-1.29). CONCLUSION: Mental health improved from pregnancy to 6 months postpartum regardless of delivery mode. Mothers with emergency cesarean section experienced more symptoms of emotional distress 6 months postpartum.

Sexual health in parous women with a history of polycystic ovary syndrome: A national cross-sectional study in Denmark.

OBJECTIVE: To examine associations between polycystic ovary syndrome (PCOS) and sexual health in midlife. METHODS: We included 31 645 mothers from the Danish National Birth Cohort who participated in a Maternal Follow up in 2013-14. A lifetime PCOS diagnosis was self-reported. Sexual health was assessed by specific sexual problems including reduced sexual desire, insufficient lubrication, difficulty in obtaining orgasm, vaginismus and pain during intercourse within the past year. We also generated a combined outcome which was positive if the women reported one or more sexual problems. Logistic regression was used to estimate adjusted odds ratios (aOR) for sexual problems with 95% confidence intervals (CI). RESULTS: Participants were on average 44 years old, and 920 women (2.9%) had ever had PCOS. One or more sexual problems were more often reported in women with PCOS compared with other women (42.6% versus 36.3%, aOR 1.29, 95% CI 1.13-1.48). Especially reduced sexual desire (25.6% versus 21.0%, aOR 1.29, 95% CI 1.10-1.50) and dyspareunia (11.4% versus 8.7%, aOR 1.34, 95% CI 1.09-1.66) were more frequent in women with PCOS. These associations were slightly weakened when further adjusting for mental and somatic health problems. CONCLUSION: Our data suggest that PCOS is linked to long-term impaired sexual health, especially reduced sexual desire and dyspareunia.

Prenatal exposure to nitrofurantoin and risk of childhood leukaemia: a registry-based cohort study in four Nordic countries.

BACKGROUND: Studies have suggested increased risks of childhood leukaemia after prenatal exposure to antibiotics, particularly nitrofurantoin. However, these findings may be related to the underlying maternal infection. This multinational study aimed to investigate the association between prenatal nitrofurantoin exposure and childhood leukaemia while accounting for maternal infection. METHODS: In a population-based cohort study of children born in Denmark, Finland, Norway or Sweden from 1997 to 2013, prenatal exposure to nitrofurantoin or pivmecillinam (active comparator) was ascertained from national Prescription Registries. Childhood leukaemia was identified by linkage to national Cancer Registries. Poisson regression was used to estimate incidence rate ratios (IRRs) and incidence rate differences (IRDs) with inverse probability of treatment weights applied to account for confounding. RESULTS: We included 44 091 children prenatally exposed to nitrofurantoin and 247 306 children prenatally exposed to pivmecillinam. The children were followed for 9.3 years on average (standard deviation 4.1). There were 161 cases of childhood leukaemia. The weighted IRR for prenatal nitrofurantoin exposure when compared with pivmecillinam was 1.34 (95% confidence interval 0.88, 2.06), corresponding to an IRD of 15 per million person-years. Higher point estimates were seen for first- and third-trimester exposure. There was no evidence of a dose-response relationship. CONCLUSIONS: Prenatal exposure to nitrofurantoin was not substantially associated with childhood leukaemia, although a slightly elevated IRR with confidence intervals including the null was observed, corresponding to a small absolute risk. The lack of a dose-response relationship and a clear biological mechanism to explain the findings suggests against a causal association.

Perinatal use of triptans and other drugs for migraine-A nationwide drug utilization study.

OBJECTIVE: To characterize nationwide utilization patterns of migraine pharmacotherapy before, during, and after pregnancy in women with triptan use. METHODS: Population-based data were obtained by linking the Medical Birth Registry of Norway and the Norwegian Prescription Database from 2006 to 2017. We included 22,940 pregnancies among 19,669 women with at least one filled triptan prescription, a proxy for migraine, in the year before pregnancy or during pregnancy. The population was classified into four groups: i) continuers; ii) discontinuers; iii) initiators, and vi) post-partum re-initiators. Participant characteristics and prescription fills for other drugs such as analgesics, antinauseants, and preventive drugs among the groups were examined, along with an array of triptan utilization parameters. RESULTS: In total, 20.0% of the women were classified as triptan continuers, 54.1% as discontinuers, 8.0% as initiators, and 17.6% as re-initiators. Extended use of triptans (≥15 daily drug doses/month) occurred among 6.9% of the continuers in the first trimester. The top 10% of triptan continuers and initiators accounted for 41% (95% CI: 39.2% - 42.5%) and 33% (95% CI: 30.3% - 35.8%) of the triptan volume, respectively. Triptan continuers and initiators had similar patterns of acute co-medication during pregnancy, but use of preventive drugs was more common among the continuers before, during, and after pregnancy. CONCLUSION: Among women using triptans before and during pregnancy, one in four continued triptan treatment during pregnancy, and extended triptan use was relatively low. Triptan discontinuation during and in the year after pregnancy was common. Use of other acute migraine treatments was higher among both continuers and initiators of triptans. Women using preventive migraine treatment were most commonly triptan continuers and re-initiators after pregnancy. Prescribing to and counseling of women with migraine should be tailored to the condition severity and their information needs to promote optimal migraine management in pregnancy.

Use of interrupted time-series analysis to characterise antibiotic prescription fills across pregnancy: a Norwegian nationwide cohort study.

OBJECTIVES: Antibiotics are the most frequently prescribed medications for pregnant and breastfeeding women. We applied interrupted time-series analysis (ITSA) to describe antibiotic prescription fills patterns in pregnant women and examined recurrent antibiotic fills in subsequent pregnancies. DESIGNS: A population-based drug utilisation study. SETTING: Norwegian primary care. PARTICIPANTS: 653 058 pregnancies derived from Medical Birth Registry of Norway linked to the Norwegian Prescription Database (2006-2016). MAIN OUTCOME MEASURE: Proportion of pregnancies exposed to antibiotics aggregated by week in pregnancy time windows. STATISTICAL ANALYSES: We descriptively analysed antibiotic prescription fills patterns and components in pregnant women. The changes in antibiotic fills in pregnancy time windows were assessed using ITSA. Interruptions points at week 4 to week 7 into pregnancy and delivery were used. Factors associated with antibiotic fills during pregnancy were identified using generalised estimating equations for Poisson regression. Recurrent antibiotic use was estimated using proportion of women who filled antibiotic prescription in a subsequent pregnancy. RESULTS: Antibiotics were filled in 27.6% pregnancies. The ITSA detected an immediate decrease of 0.07 percentage points (95% CI -0.13 to -0.01) in the proportion of exposed pregnancies at 4 weeks after conception, mainly among women taking folic acid before pregnancy. This proportion increased shortly after delivery (immediate change=1.61 percentage points (95% CI 0.31 to 2.91)) then decreased gradually afterwards (change in slope=-0.19 percentage points, 95% CI -0.34 to -0.05)). The strongest factor associated with antibiotic fills during pregnancy was having recurrent urinary tract infections (adjusted OR=2.65, 95% CI 2.59 to 2.72). Women who had filled antibiotics during a pregnancy were up to three times more likely to fill antibiotics in the subsequent pregnancies. CONCLUSIONS: ITSA highlighted important impact of pregnancy and delivery on antibiotic fillings. Having antibiotic fills in a pregnancy was associated with recurrent antibiotic fills in subsequent ones.

Mode of birth and long-term sexual health: a follow-up study of mothers in the Danish National Birth Cohort.

OBJECTIVES: To investigate the relation between mode of birth and women's long-term sexual health. DESIGN: Maternal follow-up of the Danish National Birth Cohort (1996-2002) in 2013-2014 including questions on sexual health. Logistic regression was used to relate registry-based information about mode of birth and perineal tears with data on sexual problems. SETTING: Denmark. PARTICIPANTS: Of 82 569 eligible mothers in the Danish National Birth Cohort, 43 639 (53%) completed the follow-up. Of these, 37 417 women had a partner, and answered at least one question on sexual health. MAIN OUTCOME MEASURES: Self-reported sexual health. RESULTS: Participants were on average 44 years old, and 16 years after their first birth. The frequency of sexual problems among women with only spontaneous vaginal births, the reference group, was 37%. For women who only had caesarean sections, more problems were reported (OR 1.18; 95% CI 1.09 to 1.28). For women who had a spontaneous vaginal birth subsequent to a caesarean, and for women with only vaginal births who had experienced one or more instrumental vaginal births, the odds of sexual problems did not differ from women with only spontaneous vaginal births (OR 1.00; 95% CI 0.91 to 1.11) and (OR 1.01; 95% CI 0.95 to 1.08), respectively. CONCLUSIONS: These findings indicate that caesarean section does not protect against long-term sexual problems. Rather, vaginal birth, even after caesarean section, was associated with fewer long-term sexual problems.

Use and validity of child neurodevelopment outcome measures in studies on prenatal exposure to psychotropic and analgesic medications - A systematic review.

In recent years there has been increased attention to child neurodevelopment in studies on medication safety in pregnancy. Neurodevelopment is a multifactorial outcome that can be assessed by various assessors, using different measures. This has given rise to a debate on the validity of various measures of neurodevelopment. The aim of this review was twofold. Firstly we aimed to give an overview of studies on child neurodevelopment after prenatal exposure to central nervous system acting medications using psychotropics and analgesics as examples, giving special focus on the use and validity of outcome measures. Secondly, we aimed to give guidance on how to conduct and interpret medication safety studies with neurodevelopment outcomes. We conducted a systematic review in the MEDLINE, Embase, PsycINFO, Web of Science, Scopus, and Cochrane databases from inception to April 2019, including controlled studies on prenatal exposure to psychotropics or analgesics and child neurodevelopment, measured with standardised psychometric instruments or by diagnosis of neurodevelopmental disorder. The review management tool Covidence was used for data-extraction. Outcomes were grouped as motor skills, cognition, behaviour, emotionality, or "other". We identified 110 eligible papers (psychotropics, 82 papers, analgesics, 29 papers). A variety of neurodevelopmental outcome measures were used, including 27 different psychometric instruments administered by health care professionals, 15 different instruments completed by parents, and 13 different diagnostic categories. In 23 papers, no comments were made on the validity of the outcome measure. In conclusion, establishing neurodevelopmental safety includes assessing a wide variety of outcomes important for the child's daily functioning including motor skills, cognition, behaviour, and emotionality, with valid and reliable measures from infancy through to adolescence. Consensus is needed in the scientific community on how neurodevelopment should be assessed in medication safety in pregnancy studies. Review registration number: CRD42018086101 in the PROSPERO database.