Background
Methods
Search strategy
PICOS | Key words |
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Population: Women with established diagnosis of bipolar disorder prior to pregnancy | Bipolar disorder OR affective disorders, psychotic OR affective psychosis OR mania |
Intervention/Exposure: Pregnancy, labour and birth, and the first year post-partum | Pregnancy OR postpartum period OR delivery, obstetric OR parturition OR abortion, spontaneous OR abortion, induced OR childbirth |
Comparison: Women with bipolar disorder, not experiencing pregnancy or childbirth | Women with bipolar disorder, not experiencing childbirth |
Outcome: All maternal or infant health outcomes. Papers that compared effects of using different pharmaceutical treatments were excluded. | The terms ‘woman, fetus, neonate and infant’ |
Study design: Qualitative studies, Meta-syntheses, Surveys, Cross-sectional studies, Case reports, Experimental studies (RCTs), Quasi-experimental studies, Observational studies, Systematic reviews, Meta-analyses | Qualitative, Meta-syntheses, Surveys, Cross-sectional, Case reports, Experimental, Randomised controlled trials, Quasi-experimental, Observational, Systematic reviews, Meta-analyses |
ᅟ | ᅟ |
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Bipolar disorder AND (pregnancy OR postpartum period OR delivery, obstetric OR parturition OR abortion, spontaneous OR abortion, induced) | |
(“bipolar disorder”[MeSH Terms] OR (“bipolar”[All Fields] AND “disorder”[All Fields]) OR “bipolar disorder”[All Fields]) AND ((“pregnancy”[MeSH Terms] OR “pregnancy”[All Fields]) OR (“postpartum period”[MeSH Terms] OR (“postpartum”[All Fields] AND “period”[All Fields]) OR “postpartum period”[All Fields]) OR (“delivery, obstetric”[MeSH Terms] OR (“delivery”[All Fields] AND “obstetric”[All Fields]) OR “obstetric delivery”[All Fields] OR (“delivery”[All Fields] AND”obstetric”[All Fields]) OR “delivery, obstetric”[All Fields]) OR (“parturition”[MeSH Terms] OR “parturition”[All Fields] OR “delivery, obstetric”[MeSH Terms] OR (“delivery”[All Fields] AND “obstetric”[All Fields]) OR “obstetric delivery”[All Fields]) OR (“abortion, spontaneous”[MeSH Terms] OR (“abortion”[All Fields] AND “spontaneous”[All Fields]) OR “spontaneous abortion”[All Fields] OR (“abortion”[All Fields] AND “spontaneous”[All Fields]) OR “abortion, spontaneous”[All Fields]) OR (“abortion, induced”[MeSH Terms] OR (“abortion”[All Fields] AND “induced”[All Fields]) OR “induced abortion”[All Fields] OR (“abortion“[All Fields] AND “induced”[All Fields]) OR “abortion, induced”[All Fields])) |
Quality assessment
First author, year of publication | EPHPP rating | Aim of study | Study design | Diagnostic tool | Sample | Pharmaceutic treatment | Length of follow-up | Country |
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Akdeniz 2003 [68] | M | To evaluate and emphasise the impact of clinical and psychosocial risk factors associated with pregnancy and/or the postpartum period during the course of BD in women who had given birth | Retro-spective cohort study | BD (DSM-IV). Different types are not reported. | 72 women with BD (252 pregnancies and 160 childbirths) Analysed a sub group: (n = 23): every mood episode that began during pregnancy and in postpartum period following birth at gestation 26 weeks+ | Of women with post-partum episodes (n = 26) 21 had received psychotropic medication. None of the women with post-partum episodes took Lithium during pregnancy. | Pregnancy, birth and up to one month post-partum | Turkey |
Bodén 2012 [69] | S | To investigate the risks of adverse pregnancy and birth outcomes for treated and untreated bipolar disorder during pregnancy. | Retro-spective case control study | BD (ICD-10 codes F30-31) | A cohort of 332,137 women 2005–2009. Women with a record of at least two BD diagnoses (n = 874), 320 treated with mood stabiliser, 554 untreated, compared with all other women giving birth (n = 331,263) | Treated BD with mood stabiliser (Lithium, antipsycotics or anticonvulsants) | Pregnancy and birth | Sweden |
Di Florio 2013 [73] | M | To investigate the occurrence and timing of perinatal mood episodes in women with BD-I and BD-II | Retro-spective cohort study | BD-I and BD-II (DSM- IV) | 1212 women (980 with BD-I (1404 births), 232 with BD-II (424 births) | Pharmacotherapy not reported. | Pregnancy, birth and up to one year postpartum | United Kingdom |
Di Florio 2014 [74] | M | To test the hypothesis that risk of perinatal mood episodes is greater after first pregnancy | Retro-spective cohort study | BD-I and BD-II (DSM-IV) | 1212 women (934 with BD-I (1404 births), 278 with BD-II (424 births) | No details on drug management reported. | Pregnancy, birth and up to one year postpartum | United Kingdom |
Grof 2000 [75] | M | To examine statistically the clinical course of 28 women with typical bipolar disorder, type I, who became pregnant prior to receiving successful lithium prophylaxis | Retro-spective case/control study | BD (Re-search Diagnostic Criteria, (Spitzer et al. 1978)) | 28 women with BD (56 pregnancies) and no Lithium prophylaxis; 33 childless women with BD (controls) | None had prophy-lactic Lithium during pregnancy, but 4 took Lithium for depression towards end of pregnancy. Women with acute episodes received Lithium as treatment. | Pregnancy, birth and up to 9 months postpartum | A world-wide ethnic popul-ation (the majority from Canada). |
Jablensky 2005 [67] | M | To determine the frequency, nature, and severity of 25 obstetric complic-ations in women with affective disorders and those with no psychiatric disorder | Case control study | BD (ICD-9 codes 296.0 and 296.2–5) | 763 women with BD, 1,301 pregnancies; 1,831 women (3,129 pregnancies) with no history of mental health difficulties (controls) | No specific information on prescription of medication available. | Pregnancy and birth | Australia |
Lee 2010 [70] | S | To investigate pregnancy outcomes among women with bipolar disorder, compared with women with no history of mental illness, using nationwide population-based data | Retro-spective case control study | BD (ICD-9-CM codes 295.XX, 296.0X, 296.1X, 296.4X, 296.5X, 296.6X, 296.7X, 296.80 or 296.89) | 337 women with BD; 528,061 women with no history of mental health difficulties (controls) | Information on medical treatment not reported. | Pregnancy and birth | Taiwan |
Mei-Dan 2015 [71] | S | To evaluate the risk of adverse perinatal outcomes among pregnant women previously hospitalised for BD | Population based case control study | BD (ICD-9, ICD-10CA, DSM-IV) | 1859 women with BD; 3724 women with major depressive disorder (controls); 432,358 women with no mental illness (controls) | No information regarding medical treatment. | Pregnancy, birth and up to 27 days postpartum | Canada (Ontario) |
Munk-Olsen 2009 [72] | S | To compare mothers and nonmothers to assess whether childbirth increases the risk for psych-iatric readmission and to identify pre-dictors of psychiatric readmission during the first 12 months postpartum. | Population cohort register study, prospec-tively studied | BD (ICD-8 codes 296.19, 296.39 and 298.19. ICD-10 codes F30,F31, F34.0 and F38) | All women born in Denmark between Jan 1, 1955 and July 1, 1990 who were alive on their 15th birthday and who had at least 1 psychiatric admission during the study period: January 1, 1973, through June 30, 2005. Analysis group 2 contained 56 women with bipolar disorder | No data on pharmacological treatment available. | Postpartum up to 12 months | Denmark |
Data extraction and analysis
Results
Description of included studies
First author, year of publication | Key findings: reported by authors | Potential mechanisms suggested by authors | Key recommendations made by authors |
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Mood episodes | |||
Akdeniz 2003 [68] | In 13.9 % (n = 10), the BD illness started in the peripartum period. Twenty-three (32 %) women with BD reported at least one mood episode during pregnancy or within the first month after childbirth. Eleven mood episodes occurred in pregnancy (11 out of 252 pregnancies (4.4 %)) and which started between 2nd and 8th pregnancy months. Mean duration of episode was 5.5 weeks (SD 3.8, range 1–12). Twenty-six mood episodes occurred in the first month postnatal (26 out of 160 births (16.3 %)). Mean duration of episode was 4.5 weeks (SD 4.9, range 1–23.5). Women who had a mood episode during their 1st pregnancy, were more likely to have another episode postpartum (OR 9.6 (95 % CI, 1.002–91.964)). Women were more likely to have a postpartum mood episode after the birth of the first child. Women who had a mood episode in the 1st post-partum period were more likely to have a mood episode in the 2nd post-partum period (OR 3.6 (95 % CI, 0.257–50.330)). | Biological factors such as onset of BD at an early age, antenatal mood episode and obstetric complications appeared to influence the risk, but psychosocial factors did not. | Need rigorous prospective studies. Avoid discontinuing lithium treatment too abruptly. |
Di Florio 2013 [73] Perinatal episodes across the mood disorder spectrum | Women with BD-I: 49.8 % had a mood episode in pregnancy or the post-partum period (pregnancy 8.6 %, postpartum period within 12 months of childbirth 91.4 %). More than 20 % were affected by mania or psychotic depression in the pregnancy or the post-partum period. 25 % had an episode of non-psychotic depression. Women with BD-II: 42.2 % had a mood episode in pregnancy or the post-partum period (pregnancy 18.4 %, postpartum period within 12 months of childbirth 81.6 %). Women with BD-II had a higher incidence of any perinatal mood episode compared with women with BD-I (chi-square = 10.38, d.f. = 1, p < 0.002 (calculated by review authors). The mood episodes were significantly more common during the first month post-partum than during pregnancy (BD-I OR 44.5 95 % CI 26.9–76.0 and BD II OR 4.7 95 % CI 2.4–9.8). | Only most severe episodes were rated, so other less severe disturbances may not have been recorded; rates of BD recurrence in pregnancy may thus be artificially low. | Prospective longitudinal studies are needed. Women with BD should be informed of the risk of peri-natal BD episode. |
Di Florio 2014 [74] Mood disorders and parity | Women with BD-I: 35 % reported an episode (mania/ psychotic depression) in the first pregnancy, 20.5 % in second pregnancy and 14.6 % in subsequent pregnancies. Rates of depression were similar across all pregnancies and postpartum periods. Women with BD-II: Rates of depression: first pregnancy 46 % and second pregnancy 33 %. A significant association between parity and mood episodes within 6 weeks postpartum was found. There was no significant association between parity and mood episodes in pregnancy or later postpartum. | Women having their first baby are more anxious and stressed, due to lack of experience. Multiparous women with BD may be more aware of the possibility of postnatal episodes, and may start treatment prophylactically. | Clinical studies on the effect of parity on mood disorders should also investigate possible effect of medication reducing the risk of perinatal relapse. |
Grof 2000 [75] | Five out of 28 women had a relapse during pregnancy (18 %), all in the last five weeks of pregnancy. Seven (25 %) had a postpartum relapse: 1 to 5 times, lasting 3.5 months in average, 42 % of these were manic. Postpartum episodes were significantly more than the other two periods (before and during pregnancy). Pregnancy seemed to confer a protective effect. In pregnancy, the mean rate of recurrence was 0.14, whereas mean rate in the 9 months prior to pregnancy was 0.43 (p < 0.05). Duration was also less (mean of 0.9 weeks during pregnancy, compared with mean of 6.1 weeks before pregnancy, p < 0.01). Duration postpartum was mean 12.2 weeks compared to mean 0.9 in pregnancy, p < 0.001. | May be due to placental hormones increasing throughout pregnancy, and abrupt cessation after birth. | Stop psychotropic medication in pregnancy, but continue to monitor women. Maybe recommence medication in the last 6 weeks of pregnancy. |
Mei-Dan 2015 [71] | 3.6 % (n = 66) of BD were hospitalised for psychiatric reasons during the index pregnancy. (this is more than for the major depressive disorder group: 1.9 % (n = 69) | Women with BD need more social support | |
Munk-Olsen 2009 [72] | Women with previous diagnoses of BD, had the highest risk of readmission 10 to 19 days postpartum (RR, 37.22; 95 % CI, 13.58–102.04) compared with mothers with BD who gave birth 6 to 11 months earlier. Cumulative incidence of admission 0–3 months postpartum was 22 %. During the first postpartum year, 26.9 % of all women with BD predating childbirth were admitted. | May be due to decrease of hormones post birth. Pregnancy, a time of emotional well-being, provides protection from BD. | Women with BD who are pregnant or considering pregnancy need careful monitoring and relevant psychoeducation. |
Mood episodes (Table 4)
Mood episodes during pregnancy and post-partum in the women with BD
Mood episodes during pregnancy
Mood episodes post-partum
Admission during pregnancy
Readmission post-partum
First author, year of publication | Key findings: reported by authors | Potential mechanisms suggested by authors | Key recommendations made by authors |
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Obstetric complic-ations | |||
Jablensky 2005 [67] | Women with pre-existing BD had a significantly increased risk of obstetric complications (OR 1.13, 95 % CI = 1.02–1.25), whereas those who developed BD after the index birth were at no more risk than the women without mental health difficulties (OR 1.02, 95 % CI = 0.92–1.12) (Chi-square =157.56, df = 8, p < 0.0001). | ||
Antepartum hemorrhage | |||
Jablensky 2005 [67] | Women with BD were more likely to have antepartum haemorrhage than pregnant women with no history of mental health difficulties (adjusted OR 1.60 (95 % CI 1.11–2.32)). | Possibly due more to clustering of adverse maternal characteristics than to any one factor | Research required into environmental and genetic reproductive risks |
Placenta praevia | |||
Jablensky 2005 [67] | Women with BD were more likely to have placenta praevia than pregnant women with no history of mental health difficulties (adjusted OR 2.13 (95 % CI 1.15–3.94)). Women with pre-existing BD had a significantly increased risk of obstetric complications (OR 1.13, 95 % CI = 1.02–1.25), whereas those who developed BD after the index birth were at no more risk than the women without mental health difficulties (OR 1.02, 95 % CI = 0.92–1.12) (Chi-square =157.56, df = 8, p < 0.0001). | Possibly due more to clustering of adverse maternal characteristics than to any one factor | Research required into environmental and genetic reproductive risks. |
Gestational hypertension | |||
Lee 2010 [70] | Women with BD were more likely to have gestational hypertension (1.5 % vs. 0.5 %) than pregnant women with no history of mental health difficulties (p < 0.02). | None | None |
Gestational diabetes | |||
Lee 2010 [70] | No difference in rates of gestational diabetes between women with and without BD. | None | None |
Bodén 2012 [69] | No increased risk for gestational diabetes in either treated or untreated women with BD compared to women without BD. | ||
Induction/elective CS | |||
Bodén 2012 [69] | Instrumental birth: Women without BD 24.7 %; BD without treatment 33.0 %, AOR 1.49 (95 % CI 1.24 to 1.81); BD with treatment 34.1 %, AOR 1.39 (95 % CI 1.09 to 1.79) Caesarean birth: Women without BD 16.8 %; BD without treatment 23.5 %, AOR 1.45 (95 % CI 1.18 to 1.78); BD with treatment 25.6 %, AOR 1.56 (95 % CI 1.20 to 2.03) Non-spontaneous start of labour: Women without BD 20.7 %; BD without treatment 30.9 %, AOR 1.57 (95 % CI 1.30 to 1.90); BD with treatment 37.5 %, AOR 2.12 (95 % CI 1.68 to 2.67) | Mood stabilising treatment is not necessarily the sole reason for increased risk of adverse outcomes. | Important to balance risks between treating and not treating BD. |
Preterm birth | |||
Bodén 2012 [69] | The risk of preterm birth (before 37 weeks gestation) was increased for women with BD, both for the treated and the untreated, compared with women without BD. Women without BD 4.8 %; BD without treatment 7.6 %, AOR 1.48 (95 % CI 1.08 to 2.03); BD with treatment 8.1 %, AOR 1.50 (95 % CI 1.01 to 2.24). | None | None |
Lee 2010 [70] | Women with BD were more likely to have preterm births (14.2 % vs 6.9 %) than pregnant women with no history of mental health difficulties (AOR 2.08 (95 % CI 1.53–2.83). | Smoking could be a large part of the causation | |
Mei-Dan 2015 [71] | Preterm birth was defined as < 37 gestational weeks. Higher prevalence for BD women 11.4 %, 212 out of 1858) and the BD group together with the ‘major depressive disorder’ group with preterm birth (11.4 %, N = 405) did, together, show increased prevalence above the referent group (6.2 %, n = 27000). Crude OR for BD: 1.93 (95 % CI 1.67–2.23. Adjusted OR for BD: 1.95 (1.68–2.26) when the control group was the referent (=1.00), adjusted for: maternal age, income quintile, hypertension, venous thromboembolic disease, gestational diabetes mellitus, gestational hypertension, preeclampsia/eclampsia. Preterm birth defined as < 32 gestational weeks. BD did have increased risk. N = 34, 9.1 %. Referent group n = 4884, 1.1 %. AOR: 1.70 (95 % CI 1.16–2.48). Preterm birth defined as < 28 gestational weeks. No significant increased risk. | None | None |
Pregnancy and childbirth related issues and complications (Table 5)
Non spontaneous (artificial) start of childbirth (induction or planned caesarean section)
Gestational diabetes
Gestational hypertension
Antepartum hemorrhage
Placenta praevia
Preterm birth (before 37 weeks gestation)
Mode of birth
First author, year of publication | Key findings: reported by authors | Potential mechanisms suggested by authors | Key recommendations made by authors |
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Low birthweight | |||
Jablensky 2005 [67] | Defined as < percentage estimated birth weight < 10th percentile. Women with BD were NOT more likely to have LBW infants (9.9 % vs.9.3 %) than pregnant women with no history of mental health difficulties. This cohort included only 55 % of women with pre-existing BD, who had a significantly increased risk of obstetric complications (OR 1.13, 95 % CI = 1.02–1.25), whereas those who developed BD after the index birth were at no more risk than the women without mental health difficulties (OR 1.02, 95 % CI = 0.92–1.12) (Chi-square =157.56, df = 8, p < 0.0001). | None | None |
Lee 2010 [70] | Women with BD were more likely to have low birth weight infants (9.8 % vs.5.7 %) than pregnant women with no history of mental health difficulties (AOR 1.66 (95 % CI 1.16–2.38)). | Smoking could be a large part of the causation | Monitoring of fetus, early intervention if abnormalities are noted. |
SGA | |||
Bodén 2012 [69] | No significant results for SGA were reported for women with BD (neither for the group treated with mood stabilisers nor for those not treated). | None | None |
Jablensky 2005 [67] | No difference found in SGA in women with BD compared with those with no mental health difficulties. | None | None |
Lee 2010 [70] | Women with BD were more likely to have SGA (22.3 % vs.15.7 %) than pregnant women with no history of mental health difficulties (AOR 1.47 (95 % CI 1.14–1.91)). | Smoking could be a large part of the causation | Monitoring of fetus, early intervention if required. |
Mei-Dan 2015 [71] | Severe SGA (<3rd percentile), was not significantly elevated in BD (n = 84, 4.6 %; AOR 1.15 (95 % CI 1.05–1.42) compared with the referent group (n = 16.823, 3.9 %). SGA (<10th percentile): BD presented increased risk compared to reference group: BD: n = 258 of 1859 14.1 %, reference group n = 54 858 12.8 %. AOR 1.17 (95%CI 1.03–1.34). Adjusted for: maternal age, income quintile, hypertension, venous thromboembolic disease, gestational diabetes, gestational hypertension, pre-eclampsia/eclampsia | None | Interventions should be evaluated, to optimise health of women with BD |
LGA | |||
Mei-Dan 2015 [71] | Severe LGA (>97th percentile) was significantly more common among women with BD (n = 69, 3.8 %; AOR 1.29. 95 % CI 1.08–1.54). Reference group 2.7 %, n = 11 712. Adjusted for: maternal age, income quintile, hypertension, venous thromboembolic disease, and gestational diabetes, gestational hypertension, pre-eclampsia/eclampsia LGA (>90th percentile) was NOT significantly more common. BD 167 of 1859 9.1 % compared to referent without mental illness n = 35,158 8.2 %. AOR 1.13 (0.96.1.32). | None | Interventions should be evaluated, to optimize health of women with BD |
Congenital anomalies | |||
Bodén 2012 [69] | Congenital malformations in infants born to women: without BD: 2.0 %; with BD without treatment with mood stabilisers: 1.9 %; with BD with treatment with mood stabilisers: 0 to 3.5 %, depending on the drug used, average 3.4 % (Numbers calculated by this review team). | None | None |
Jablensky 2005 [67] | No difference found in congenital abnormalities in women with BD compared with those with no mental health difficulties. | None | None |
Mei-Dan 2015 [71] | BD did present increased risk for congenital anomalies. BD n = 90, 0.5 %. Referent group n = 14 963, 3.5 %. AOR: 1.48 (95 % CI 1.20–1.82) Adjusted for: maternal age, income quintile, hypertension, venous thromboembolic disease, gestational diabetes, gestational hypertension, pre-eclampsia/eclampsia | None | None |
Neonatal re-admissions | |||
Mei-Dan 2015 [71] | Neonatal admission, < 28 days of life. BD did have increased risk. N = 36, 2.0 % compared to referent n = 3953, 0.9 %. AOR: 2.41 (95 % CI 1.76–3.31) Adjusted for: maternal age, income quintile, hypertension, venous thromboembolic disease, and gestational diabetes, gestational hypertension, pre-eclampsia/eclampsia | None | None |
Fetal distress | |||
Jablensky 2005 [67] | No difference in fetal distress, cephalopelvic disproportion, atypical presentation, or cord anomalies, threatened preterm labor, early rupture of the membranes, prolonged labour, low 5-min Apgar scores, neonatal mortality in women with BD compared with those with no mental health difficulties. | None | None |
Boden 2012 [69] | Showed no difference in low Apgar scores between women without BD and those untreated (AOR 1.56, 95 % CI = 0.85–2.86) and treated (AOR 0.88, 95 % CI = 0.33–2.34) for BD. | None | None |
Stillbirth | |||
Jablensky 2005 [67] | No difference found in stillbirths in women with BD compared with those with no mental health difficulties. | None | None |
Mei-Dan 2015 [71] | BD did not present increased risk for stillbirth. BD n = 11, 0.6 %. Referent group n = 2235, 0.5 %. AOR 1.20 (95 5 CI 0.66–2.18), adjusted for: maternal age, income quintile, hypertension, gestational diabetes, gestational hypertension, venous thromboembolic disease, preeclampsia | None | None |
Infant mortality | |||
Mei-Dan 2015 [71] | Infant mortality < 28 days of life. BD did not have increased or reduced risk N = ≤ 5, referent group n = 1004, 0.2 %. AOR: 0.72 (0.23–2.23). Mortality <1 year of life. No difference in risk BD n = 7, 0.4 % referent group n = 1389, 0.3 %. AOR: 0.99 (95 % CI 0.44–2.22) | None | None |
Neonatal morbidity | |||
Mei-Dan 2015 [71] | Secondary outcome; neonatal morbidity defined as RDS (respiratory distress syndrome), Seizure, sepsis, IVH (Intravenous hyperalimentation), persistent fetal circulation, and neonatal abstinence syndrome. 1. Any of these neonatal morbidities: BD had increased risk: n = 96, 5.4 %. Referent group (without mental illness) n = 8270, 1.9 %. AOR 2.99 (95 % CI 2.44–3.66) 2. RDS: BD had increased risk. N = 26, 1.5 %. Referent group: n = 4049, 1.0 %. AOR 1.64 (95 % CI 1.13–2.39) 3. Seizure: BD had increased risk. BD n = 10. 0.6 %, referent group n = 844, 0.2 %. AOR = 2.54 (95%CI 1.31–4.90). 4. Sepsis: BD had increased risk. BD n = 23, 1.3 %, referent group 3178, 0.7 %. AOR: 1.80 (95 % CI 1.20–2.70) 5. IVH: BD had increased risk. BD n = 13, 0.7 %. Referent group n = 1485, 0.3 %. AOR: 2.12 (95 % CI 1.22–3.67). 6. Persistent fetal circulation. BD did NOT have increased risk. BD n = ≤ 5, referent group n = 615, 0.1 %. AOR: 1.89 (95 % CI 0.78–4.58). 7. Neonatal abstinent syndrome. BD had severe increased risk. BD n = 70, 1.9 %. Referent group n = 177, 0.0 %. AOR = 52.2 (95 % CI 36.5–74.7)Adjusted for: maternal age, income quintile, hypertension, venous thromboembolic disease, gestational diabetes, gestational hypertension, pre-eclampsia/eclampsia | None | None |