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.

ObjectivesAntibiotics 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.DesignsA population-based drug utilisation study.SettingNorwegian primary care.Participants653 058 pregnancies derived from Medical Birth Registry of Norway linked to the Norwegian Prescription Database (2006–2016).Main outcome measureProportion of pregnancies exposed to antibiotics aggregated by week in pregnancy time windows.Statistical analysesWe 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.ResultsAntibiotics 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.ConclusionsITSA 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.

ObjectivesTo investigate the relation between mode of birth and women’s long-term sexual health.DesignMaternal 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.SettingDenmark.ParticipantsOf 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 measuresSelf-reported sexual health.ResultsParticipants 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.ConclusionsThese 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.

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;, 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.

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.