Psychopharmacology and Pregnancy: Treatment Efficacy, Risks, and Guidelines 2014

8. Bipolar Disorder, Psychopharmacology, and Pregnancy

Martien Snellen  and Gin S. Malhi2, 3, 4


Mercy Hospital for Women, Heidelberg, Australia


Department of Psychiatry, University of Sydney, Sydney, Australia


CADE Clinic, Royal North Shore Hospital, Sydney, Australia


Mood Disorders Unit, Northside Clinic, Ramsay Healthcare, Sydney, Australia

Martien Snellen


8.1 Bipolar Disorder in Women

8.2 Bipolar Disorder in Pregnant Women

8.3 Treatment of Bipolar Disorder in Pregnancy

8.4 Safety of Specific Treatments for Bipolar Disorder in Pregnancy

8.5 Lithium Safety in Pregnancy

8.6 Anticonvulsant Safety in Pregnancy

8.7 Antipsychotic Safety in Pregnancy

8.8 Specific Clinical Considerations and Recommended Monitoring

8.9 Lithium: Monitoring in Pregnancy

8.10 Anticonvulsants: Monitoring in Pregnancy

8.11 Antipsychotics: Monitoring in Pregnancy

8.12 Summary of Pregnancy Monitoring for Mood Stabilisers and Antipsychotics (Adapted from Galbally et al. , , )

8.13 Recommendations for the Treatment of Women with Bipolar Disorder in Pregnancy



The antenatal management of women with bipolar disorder presents a major challenge for both obstetric and mental health services due to the inherent risks associated with both the condition and its treatment: each of which can be considered to be teratogenic in their own right. The possibility of pregnancy in all women of reproductive age should be considered when making treatment decisions from the outset, especially given that unplanned pregnancy is particularly common in this patient group. For all women with bipolar disorder it is essential that specific considerations be attended to, and monitoring systems established and followed perinatally.


Bipolar disorderPsychophamacologyPregnancyGuidelines

The antenatal management of women with bipolar disorder presents a major challenge for both obstetric and mental health services due to the inherent risks associated with both the condition and its treatment: each of which can be considered to be teratogenic in their own right. The possibility of pregnancy in all women of reproductive age should be considered when making treatment decisions from the outset, especially given that unplanned pregnancy is particularly common in this patient group. For all women with bipolar disorder it is essential that specific considerations be attended to, and monitoring systems established and followed perinatally.

With a lifetime prevalence for bipolar disorder of around 1 %, increasing fertility rates within this population due in part to both the success of modern treatments and the prolactin sparing options available, and the tendency to manifest during the reproductive years, all clinicians will at some time need to consider the inherent risks of treatment and non-treatment in the perinatal setting. Specifically, prevalence differs across age cohorts peaking in the 18–24 age group (0.9 %) and dropping to its lowest in those 55 and over (0.1 %).

Bipolar disorder is frequently a recurrent, disabling illness with most people suffering many episodes (an average of 0.4–0.7 per year), each lasting 3–6 months (Angst and Selloro 2000), with only 50 % achieving syndromic recovery, 25 % symptomatic and functional recovery (Keck et al. 1998), and a suicide rate 15 times that of the general population (Harris and Barraclough 1997). High rates of serious comorbid medical conditions that go unrecognised (Feldman et al. 2012) and high treatment noncompliance rates (Colom et al. 2000) confound the risks further.

The perinatal period has long been recognised to represent a period of significant relapse risk for women who suffer from bipolar disorder; however, increasingly we are becoming aware that this is not only due to inherent risks, but also to precipitous cessation of pharmacological treatment during pregnancy and breastfeeding. Treatment guidelines written for the general population frequently ignore these risks by advising tapered medication withdrawal if a pregnancy is contemplated or confirmed, possibly due to medico-legal considerations as well as a desire to avoid potential adverse foetal development effects. With the average pregnancy taking up to 1 year to conceive, and pregnancy lasting around 9 months, this leaves open a significant window of opportunity for relapse or psychosocial deterioration to occur. More recent publications focus more on the process of obtaining informed consent and adequate obstetric and psychiatric monitoring in recognition of the fact that most women with bipolar disorder require maintenance treatment during their pregnancies (Galbally et al. 2010ab).

8.1 Bipolar Disorder in Women

About 65 % of patients with bipolar disorder have a co-morbid psychiatric or physical condition (Sasson et al. 2003) and it has been reported that this is 2.7 times more likely to be the case in women than men (Strakowski et al. 1992). Gender differences have also been reported that suggest women are also more likely to experience a rapid cycling pattern of illness and mixed episodes, have a greater latency before treatment with maintenance treatment, and follow a depressive diathesis in their illness course (Barnes and Mitchel 2005). All of which potentially elevate the overall risks within the perinatal setting.

Furthermore, there is considerable evidence that cessation of lithium is associated with a significantly elevated risk of relapse in the general bipolar population (Biel et al. 2007) and that the majority of relapses occur within 3 months of discontinuation (Suppes et al. 1991; Cavanagh et al. 2004) and that this phenomenon extends to withdrawal of other mood stabilisers (Franks et al. 2008).

8.2 Bipolar Disorder in Pregnant Women

Unfortunately, there remains a distinct lack of clarity regarding the natural course of bipolar disorder in pregnancy. It has been proposed that this altered physiological and psychological state may exert a favourable effect on the course of the illness (Grof et al. 2000); however, more recent studies suggest an elevated recurrence rate (Freeman et al. 2002; Viguera et al. 2011). Others have found that up to a half of women with bipolar disorder report an exacerbation of their symptoms during pregnancy (Blehar et al. 1998). This likely reflects a number of pathophysiological processes and alterations in oestrogen levels and inflammatory processes, and fluctuations in biorhythms and functioning are currently under investigation as potential aetiological triggers.

In a prospective study that examined the effects of mood stabiliser cessation during pregnancy those women with bipolar disorder were more than twice as likely to relapse in pregnancy (85.5 % vs. 37 %), with the majority of episodes being either depressive or mixed dysphoric states, and were unwell for five times longer than those who continued their medication (Viguera et al. 2007). These observations suggest that pregnancy needs to be regarded as a high-risk period for relapse, particularly in the setting of discontinuation of maintenance treatment, and that perhaps the very “nature” of bipolar disorder, as it manifests in women, further complicates matters.

But in practice how do we differentiate those women with bipolar disorder who need pharmacological intervention in pregnancy and those who do not? A number of pharmacological treatment guidelines have been established in order to inform decision-making. However, methodological differences between evidence-based and consensus-based guidelines add as much confusion as they do clarity. Furthermore, the suggested algorithms can change dramatically when evidence regarding teratogenicity is prioritised over evidence for treatment efficacy. For instance, the National Institute for Health and Clinical Excellence (NICE) guidelines support the use of anticonvulsants and lithium as first-line treatment agents in the non-pregnant population due to their established evidence base, but withdraw this recommendation in the pregnant population where they prefer second-generation antipsychotics that have a less established evidence base for efficacy (NICE 2006). Given that the overall success rate for pharmacological treatment in bipolar disorder is moderate at best, we suggest that the best treatment option is usually the one that works for any particular patient. This also raises the issue of whether the mother’s health should take precedence over that of the child? However, should discontinuation of mood stabilising medication be contemplated, there is universal acceptance that it should be slowly tapered and abrupt withdrawal avoided.

Bipolar disorder is not only heterogeneous in its acute manifestations, but also in its longitudinal course. A clinician will need to consider many individual factors prior to making any recommendations regarding prophylactic treatment: number and severity of relapses, severity of psychotic episodes, co-morbidity, previous treatment response or non-response to any particular agent, side effects, family history of bipolar disorder, previous suicidality, residual symptoms, ongoing stressful life events or poor social support, age of onset, and time intervals between episodes. There also remains a lack of consensus as to the duration of long-term treatment with the NICE guidelines recommending maintenance for up to 5 years for patients with risk factors for relapse, whereas the other evidence-based guidelines such as those developed by the World Federation of Societies of Biological Psychiatry (WFSBP), the British Association for Psychopharmacology (BAP), and the Canadian Network for Mood and Anxiety Treatments (CANMAT) recommend lifelong treatment (Samalin et al. 2013).

A recent publication has added significantly in our endeavour to prevent postpartum psychosis and mania in women at high risk by recommending prophylactic treatment immediately postpartum in those women who have a history of psychosis limited to the postpartum period, to avoid in utero foetal exposure to medication, and continuous prophylaxis throughout pregnancy and the postpartum period to reduce peripartum relapse risk in women with bipolar disorder (Bergink et al. 2012). What has in effect been achieved here is a realisation that not all episodes of puerperal psychosis are necessarily an episode of bipolar disorder.

Given that it is now clear that in the majority of cases treatment with maintenance psychotropics throughout pregnancy is required, it has been suggested that the question is not whether “to treat or not to treat?” but instead “how to treat optimally?”(Gentile 2012a). With this in mind we consider the treatment of bipolar disorder in pregnancy.

8.3 Treatment of Bipolar Disorder in Pregnancy

The Developmental Origins of Health and Disease paradigm (DOHaD) suggests that pregnancy and infancy are critical periods of growth and development that have lifelong implications (Gluckman et al. 2008). Untreated bipolar disorder has been linked with increased risks of pregnancy complications such as preterm birth, low birth weight and Apgar scores, induced labour, caesarean section, and instrumental delivery, and neonatal microcephaly and hypoglycaemia (Jablensky et al. 2005; Lee and Lin 2010; Bodén et al. 2012). Offspring of women with bipolar disorder have been shown to have increased rates of memory and attention disturbance as well as emotional, social, and behavioural problems. It has been proposed that both microcephaly and recurrent neonatal hypoglycaemia may be aetiological in this regard (Gentile 2012a). It remains unclear as to whether adequate maintenance treatment throughout pregnancy attenuates these risks. Of greatest concern, however, is the fact that within the obstetric setting there is an extremely low rate of case identification (Spitzer et al. 2000).

Standard treatment of bipolar disorder includes lithium, the anticonvulsants sodium valproate, carbamazepine, and lamotrigine, and increasingly second-generation antipsychotics. The aim is always to achieve the minimum effective dose; however, the emphasis needs to be on effective rather than minimal, and this is often not the case. It can be argued that “half treatment” represents the worst possible scenario as it exposes the foetus to both the risks of treatment and maternal mental illness. Despite evidence that polypharmacy increases the overall teratogenic risk (Burt et al. 2010); many patients who would otherwise remain symptomatic cannot afford the luxury of monotherapy. There is also the possibility that increased dosing frequency can offer advantage through minimising peak plasma levels, although compliance issues need to be taken into consideration. Essentially, a risk-free scenario does not exist. It is rather a matter of harm minimisation, informed consent, and careful monitoring of mental health as well as maternal physiological and foetal anatomical parameters.

Psychotherapy remains an essential adjunct to pharmacotherapy in the treatment of all forms of mental illness. Despite the paucity of research into the direct and indirect effects of non-pharmacological treatments for bipolar disorder, it is widely accepted that psychotherapy assists overall improved psychosocial functioning (Scott 2006) and a healthy therapeutic alliance is an essential component of care. Attention needs to be paid to life and lifestyle stressors, sleep preservation, the establishment of realistic expectations, early warning signs for relapse, support structures, and pathways to care.

8.4 Safety of Specific Treatments for Bipolar Disorder in Pregnancy

Inevitably, at some point, difficult decisions need to be made and ideally these should involve a collaborative approach between clinician and patient. It is essential that a process of obtaining informed consent be followed and patient preference be involved in the decision-making process. A comprehensive risk:benefit analysis needs to consider both the risks of treatment and also those associated with non-treatment for both mother and child. Consideration needs to be given to the risks of teratogenesis, obstetric complications, impairment of neonatal adaption, and negative long-term neurodevelopmental or other health outcome. Once decisions are made and enacted a comprehensive plan for obstetric, paediatric, and psychiatric monitoring needs to be put in place that considers the unique challenges that exist within the perinatal setting.

It has been estimated that at least 500 cases are needed to determine differences in occurrence of major malformation and larger numbers are required to adequately control for other variables (Meador et al 2008). To date, only some of the anticonvulsants have been adequately investigated in this regard. There is a reasonable body of data regarding the potential risks associated with the use of lithium in pregnancy; however, much of our comfort in prescribing antipsychotics during pregnancy comes from the absence of negative data rather than the presence of positive data. The issue is further complicated by the fact that the majority of studies that aim to evaluate and clarify teratogenic risk associated with antenatal exposure to psychotropic medications were not designed to control for possible teratogenic effects of the underlying bipolar disorder. We eagerly await further clarity from current prospective registry studies that include a non-treatment control group.

8.5 Lithium Safety in Pregnancy

Lithium remains a gold standard treatment for bipolar disorder; however, initial retrospective reports identified an elevated risk of cardiac malformation, in particular Ebstein’s anomaly that is characterised by downward displacement of the tricuspid valve into the right ventricle and variable levels of right ventricular hypoplasia (Schou et al. 1973). More recent research has downgraded the overall concern with the estimated incidence being 0.05–0.1 % which represents 20–40 times the general population risk (Cohen et al. 1994). There is also some suggestion that lithium may be associated with a slightly increased risk of neural tube defect (Gentile 2012b). However, a recent systematic review and meta-analysis of lithium’s toxicity profile recorded no significant increased risk of congenital malformation (McKnight et al. 2012).

Lithium demonstrates complete placental passage and equilibrates between maternal and foetal circulations, and adverse perinatal outcomes are more extensive when concentrations are higher at delivery (Newport et al. 2005). Exposure has been associated with an increased risk of diabetes insipidus, polyhydramnios, thyroid dysfunction, floppy baby syndrome and cardiac rhythm disturbances in the newborn (Llewellen et al. 1998; Gentile 2012b); however, most of these concerns arise from case reports. Lithium-exposed babies are more likely to be large for dates and this does not appear to be a dose-related effect (Jacobson et al. 1992; Troyer et al. 1993).

There is extremely sparse information regarding infant neurodevelopmental outcomes following in utero exposure to lithium; however, that which is available is reassuring in that no difference has been identified between exposed and non-exposed infants (Jacobson et al. 1992; Schou 1976; van der Lugt et al. 2012).

Whilst certain guidelines recommend that lithium exposure during the first trimester is a contraindication (e.g. NICE 2006) it is now widely acknowledged that the actual overall teratogenic risk is both significantly less than first presumed and certainly less in comparison to a number of alternatives (i.e. the anticonvulsants sodium valproate and carbamazepine). In a highly select patient population first trimester exposure can be avoided only after a clinical judgment is made regarding the potential risk of relapse secondary to discontinuation.

8.6 Anticonvulsant Safety in Pregnancy

Most studies into structural malformation and neurocognitive development in women receiving anticonvulsants have focused on women treated for epilepsy rather than bipolar disorder and this introduces potential confounding factors such as genetic predisposition and an independent effect of seizures. Hence, it is only in the last decade or so that some clarity has emerged regarding such risk.

Anticonvulsants are clear teratogens and a recent review of prospective registry data suggests malformation rates of 2.7 % for lamotrigine, 2.9 % for carbamazepine, and 8.7 % for sodium valproate (Walker et al. 2009). The majority of structural abnormalities relate to central nervous system anomalies, particularly neural tube defects (5–9 % for sodium valproate and 0.5–1 % for carbamazepine), as well as cardiac, facial, limb, and urogenital malformations (Yonkers et al. 2004). With sodium valproate there appears to be a dose-related effect with the risk of malformation rising most dramatically with doses above 1,000 mg per day (Morrow et al. 2006); however, this is potentially the case with all anticonvulsants (Tomson et al. 2011). A pattern of specific facial abnormalities has been suggested for both sodium valproate and carbamazepine with mid-face hypoplasia, short nose with anteverted nostrils, and long upper lip (Jones et al. 1989). Carbamazepine has also been associated with reductions in birth weight (of about 250g) and mean head circumference (Diav-Citrin et al. 2001; Hiilesmaa et al. 1981). There have also been conflicting reports regarding a slightly elevated risk of orofacial cleft with lamotrigine (Hunt et al. 2009).

Neonatal complications appear to be most problematic with sodium valproate with reports of elevated risks for heart rate decelerations, withdrawal symptoms such as irritability, jitteriness, abnormal tone, feeding difficulties, and hepatotoxicity, hypoglycaemia, and reduction in fibrinogen. Carbamazepine and lamotrigine have been associated with hepatotoxicity and the latter with the potential for Stevens–Johnson syndrome in the infant (Yonkers et al. 2004).

The anticonvulsants are increasingly being studied with regard to their potential to cause adverse neurodevelopmental outcomes following in utero exposure. Both carbamazepine and lamotrigine have not been associated with any later developmental delay or IQ reduction; however, sodium valproate is clearly teratogenic in this regard and a clear association has been demonstrated between in utero exposure and reduced IQ scores, impaired verbal acquisition, increased frequency of maladaptive behaviour, as well as global neurodevelopmental delay (Meador et al. 2007; Bromley et al. 2013). The risk of adverse neurodevelopmental outcome appears to be dose dependent and further worsened when used in combination with other anticonvulsants.

Essentially, unless absolutely necessary, sodium valproate should be avoided throughout pregnancy as well as first trimester exposure to the other mood stabilising anticonvulsants. Whilst this represents the ideal, it needs to be recognised that not all patients can be afforded this luxury given the high risk of relapse in those women with bipolar disorder who discontinue maintenance treatment during pregnancy.

8.7 Antipsychotic Safety in Pregnancy

At this point in time any comfort we may have in prescribing antipsychotics during pregnancy comes from the absence of negative data rather than the presence of positive data. Slowly, encouraging data is emerging from pregnancy registries that follow a prospective design. A recent review identified only seven studies on pregnancy outcomes and antipsychotic exposure and no clear association with any specific malformation has emerged (Einarson and Boskovic 2009). However, a further systematic review of antipsychotic therapy during early and late pregnancy concluded that presently we are unable to adequately advise regarding malformation risk secondary to in utero exposure to atypicals (Gentile 2010).

Antipsychotic medications have been associated with both low birth weight and large-for-dates babies, the latter mainly associated with exposure to atypicals (Newham et al. 2008). Hypertonicity, tremulousness, and poor motor maturity in neonates have been observed in typical antipsychotics (Auerbach et al. 1992). However, it remains unclear to what extent atypical antipsychotics may complicate the neonatal period and it is recommended that observation should occur for transient extra-pyramidal side effects, withdrawal, and sedation (Galbally et al. 2010ab).

Recent studies that follow prospective case-controlled designs have found an association between in utero exposure to atypical antipsychotics and reduced neuromotor performance; in particular delays were observed in cognition, motor skill, and social-emotional and adaptive behavioural domains (Peng et al. 2013; Johnson et al. 2012). Encouragingly the suggestion is that exposure increases the risk of delay not permanent impairment; however, further studies with longer follow-up periods are required. Infant outcomes were also negatively associated with indices of maternal mental illness and it is likely that adverse effects on subsequent infant neurodevelopment are influenced by both maternal mental illness and foetal exposure to antipsychotics, and these effects may be additive.

8.8 Specific Clinical Considerations and Recommended Monitoring

Unless otherwise referenced the following recommendations have been derived from previous publications by Galbally et al. (2010ab2011):

Given the high risk of unrecognised physical comorbidity in women who suffer from bipolar disorder it is recommended that a baseline organic screen be performed as a matter of course. Investigations should include full blood examination, renal, thyroid, and hepatic function testing, estimations of iron, vitamin B12, folate, and vitamin D, fasting glucose, and serum lipids, in addition to the usual obstetric investigations. Consideration should also be given to ECG examination if a patient is taking a medication that could compromise the QT interval.

As most medications used to treat bipolar disorder carry an elevated risk of foetal malformation it is recommended that high-resolution ultrasounds that focus in particular on neural tube and cardiac and facial structures be performed at 12 and 20 weeks gestation.

Changes in gastric emptying, increased volume of distribution, decreased gastrointestinal motility, decreased drug-binding capacity, and increased hepatic metabolism during pregnancy frequently alter the therapeutic dose of all psychotropic medications. Increased frequency of serum level estimation of lithium and the anticonvulsants is recommended as well as increased frequency of psychiatric review.

Folate, administered at a dose of 5 mg daily, is recommended for all pregnant women who take mood stabilisers or antipsychotics, or those contemplating pregnancy as it may reduce the risk of various birth defects: although this suggestion remains controversial (Lassi et al. 2013; Sotres-Alvarez et al. 2013). Ideally it should be commenced 3 months prior to conception and continued throughout pregnancy, particularly in women who take anticonvulsants that can adversely influence folate metabolism. Similarly, given the high rates of inadequate nutrition and self-care in this patient population, multivitamins specifically formulated for pregnancy are also recommended.

A written individualised Perinatal Mental Health Care Plan should be prepared for each mother and baby and placed in a prominent position within the case file. It should outline: the current treatment team, all pharmacological and other treatments (including dose recommendations across the peripartum), a plan for mode of infant feeding and avoidance of pharmacological lactation suppressants (as they may precipitate relapse), recommendations for support, rest and sleep preservation within a low stimulus environment, recommendations regarding minimum length of stay, plans for regular psychiatric and paediatric review, and a comprehensive discharge plan that ideally includes support for the mother, partner, mother–infant relationship, early parenting skills, and establishment of pathways to care should relapse occur.

8.9 Lithium: Monitoring in Pregnancy

Given the physiological changes that occur in pregnancy lithium levels require careful monitoring throughout, but particularly in the third trimester and this is over and above the usual requirements (Malhi et al. 2012). This should include monthly serum estimations throughout pregnancy increasing to weekly after 36 weeks gestation. Thyroid and renal function should also be measured during each trimester as well as serum calcium early in pregnancy. In order to be consistent with the table presented later.

Ultrasound assessment that focuses on nuchal translucency should be performed at 12 weeks, followed by high-resolution ultrasound and Doppler flow studies for early cardiac assessment at 16 weeks, and a morphological scan with specific attention to foetal echocardiography performed at 20 weeks gestation. As there is an increased risk of babies being large for dates all lithium-exposed pregnancies should be monitored for growth through scanning during the third trimester.

Wherever possible, lithium should be ceased 24–48 h prior to delivery and reinstated post delivery at pre-pregnancy dose. Adequate hydration needs to be ensured during labour and consideration given to intravenous hydration when necessary. Nephrotoxins such as aminoglycosides and nonsteroidal anti-inflammatory drugs need to be avoided, and cord blood taken for lithium level and renal and thyroid function estimation. The neonate needs to be carefully monitored for any evidence of lithium toxicity or withdrawal. It is further recommended that a mother does not breastfeed whilst taking lithium.

8.10 Anticonvulsants: Monitoring in Pregnancy

Women treated with sodium valproate, carbamazepine, and lamotrigine should have an ultrasound at around 12 weeks gestation. Early signs of anencephaly should be recognised at this gestation and the nuchal translucency measurement further offers a useful screening for cardiac and other structural malformations. A mid-trimester morphology scan that pays particular attention to the neural axis, heart, and face should be performed in preference to maternal serum alpha-fetoprotein estimation that is much less reliable. Similarly, adequate review of foetal growth (preferably through growth scanning at 28 and 34 weeks and further as indicated) is recommended.

Serum level estimations of anticonvulsants should be performed monthly throughout pregnancy. In particular, lamotrigine levels are highly variable during pregnancy and clinically significant fluctuations in drug concentrations have been observed (Patsalos et al. 2008; Clark et al 2013). Similarly, serum lamotrigine levels can rise dramatically postpartum, introducing the possibility of toxicity if dose adjustments are not made (Clark et al. 2013). Hepatic function estimations should also be performed each trimester for those women who take sodium valproate and carbamazepine, as well as a platelet count for those on sodium valproate.

At birth Konakion should be administered to all newborns exposed to the enzyme inducers carbamazepine and sodium valproate in order to minimise the risk of neonatal bleeding and the neonate observed for any evidence of toxicity or withdrawal, and a careful morphological examination performed.

8.11 Antipsychotics: Monitoring in Pregnancy

Given the potential for increased risk of metabolic syndrome and gestational diabetes with atypical antipsychotics it has been suggested that glucose tolerance testing, rather than glucose challenge testing, should be performed early in the second trimester (14–16 weeks) and at 28 weeks gestation. Similarly, adequate review of foetal growth (preferably through growth scanning at 28 and 34 weeks and further as indicated) is essential given the increased risk of abnormal birth weight.

Ultrasound assessment that focuses on nuchal translucency should be performed at 12 weeks, followed by a high-resolution morphology scan performed at 20 weeks gestation. As there is an increased risk of babies being either large for dates or small for dates all antipsychotic-exposed pregnancies should be monitored for growth through scanning during the third trimester.

Neonates should be observed for any evidence of toxicity, withdrawal, sedation, and extra-pyramidal side effects.

8.12 Summary of Pregnancy Monitoring for Mood Stabilisers and Antipsychotics (Adapted from Galbally et al. 2010ab2011)


All mood stabilisers and antipsychotics

Lithium carbonate



First trimester

FBE, U&E, LFT, TFT, iron studies, vitamin D, B12, folate

High-resolution ultrasound with focus on NT at 12 weeks gestation

Monthly serum level


Monthly serum level

BMI, fasting glucose, and lipids, ECG

Second trimester

High-resolution morphology scan at 20 weeks gestation.

Growth monitoring

Monthly serum level

Fetal Echocardiography and Doppler Flow Studies at 16 weeks gestation.


Monthly serum level

Platelet count, LFT

Early GTT at 14–16 weeks gestation

Weight, BP

Third trimester

Growth Scans at 28 and 34 weeks gestation

Monthly serum level and then weekly from 36 weeks


Monthly serum level

Platelet count, LFT

Weight, BP

Repeat GTT at 28 weeks gestation

After delivery

Observe neonate for toxicity, withdrawal, and sedation

Careful morphological examination

Maternal serum level, U&E, TFT

Cord blood lithium level, TFT, U&E

Serum level

Platelet count, LFT

Administer Konakion to valproate- or carbamazepine-exposed neonates

Observe neonate for EPSE

8.13 Recommendations for the Treatment of Women with Bipolar Disorder in Pregnancy














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