Abstract Introduction Patients with bipolar affective disorder can be effectively managed with pharmacological intervention. This case report describes a pregnant woman with a ten-year history of bipolar affective disorder that was being treated with lithium, haloperidol and benztropine. Case presentation The patient had a normal pregnancy, but developed an elevated blood pressure and started to lose weight at 36 weeks of gestation. During pregnancy, plasma concentrations of choline and phosphatidylcholine are increased to meet the demands of the foetus. However, our findings in this case included depletion of plasma choline and phosphatidylcholine concentrations. Other unusual outcomes included low placental weight and low infant birth weight. Conclusion This report suggests that the pharmacological management of this patient could possibly account for the findings.</p

A Postle

AA Leaf

AG Mallinger

AV Jablensky

CD Albright

HM Ehrenberg

Horace Fletcher

M Haag

M Thame

Maxine Gossell-Williams

O Pleul

RH Wu

SH Zeisel

Steven H Zeisel

SW Patton

Y Ozarda Ilcol

English

PubMed

Crossref

Unexpected depletion in plasma choline and phosphatidylcholine concentrations in a pregnant woman with bipolar affective disorder being treated with lithuim, haloperidol and benztropine: a case report

Springer - Publisher Connector

Abstract Introduction Patients with bipolar affective disorder can be effectively managed with pharmacological intervention. This case report describes a pregnant woman with a ten-year history of bipolar affective disorder that was being treated with lithium, haloperidol and benztropine. Case presentation The patient had a normal pregnancy, but developed an elevated blood pressure and started to lose weight at 36 weeks of gestation. During pregnancy, plasma concentrations of choline and phosphatidylcholine are increased to meet the demands of the foetus. However, our findings in this case included depletion of plasma choline and phosphatidylcholine concentrations. Other unusual outcomes included low placental weight and low infant birth weight. Conclusion This report suggests that the pharmacological management of this patient could possibly account for the findings.</p

Gossell-Williams Maxine

Fletcher Horace

Zeisel Steven H

Directory of Open Access Journals

Journal of Medical Case Reports

Abstract Introduction Patients with bipolar affective disorder can be effectively managed with pharmacological intervention. This case report describes a pregnant woman with a ten-year history of bipolar affective disorder that was being treated with lithium, haloperidol and benztropine. Case presentation The patient had a normal pregnancy, but developed an elevated blood pressure and started to lose weight at 36 weeks of gestation. During pregnancy, plasma concentrations of choline and phosphatidylcholine are increased to meet the demands of the foetus. However, our findings in this case included depletion of plasma choline and phosphatidylcholine concentrations. Other unusual outcomes included low placental weight and low infant birth weight. Conclusion This report suggests that the pharmacological management of this patient could possibly account for the findings

Gossell-Williams, Maxine

Fletcher, Horace

Zeisel, Steven H.

Carolina Digital Repository

BioMed CentralJournal of Medical Case ReportsssOpen AcceCase reportUnexpected depletion in plasma choline and phosphatidylcholine concentrations in a pregnant woman with bipolar affective disorder being treated with lithuim, haloperidol and benztropine: a case reportMaxine Gossell-Williams*1, Horace Fletcher2 and Steven H Zeisel3Address: 1Department of Basic Medical Sciences, University of the West Indies, Jamaica, 2Department of Obstetrics, Gynaecology and Child Health, University of The West Indies, Jamaica and 3Department of Nutrition, School of Public Health and School of Medicine University of North Carolina at Chapel Hill, NC 27599, USAEmail: Maxine Gossell-Williams* - maxine.gossell@uwimona.edu.jm; Horace Fletcher - horace.fletcher@uwimona.edu.jm; Steven H Zeisel - steven_zeisel@unc.edu* Corresponding author    AbstractIntroduction: Patients with bipolar affective disorder can be effectively managed withpharmacological intervention. This case report describes a pregnant woman with a ten-year historyof bipolar affective disorder that was being treated with lithium, haloperidol and benztropine.Case presentation: The patient had a normal pregnancy, but developed an elevated bloodpressure and started to lose weight at 36 weeks of gestation. During pregnancy, plasmaconcentrations of choline and phosphatidylcholine are increased to meet the demands of thefoetus. However, our findings in this case included depletion of plasma choline andphosphatidylcholine concentrations. Other unusual outcomes included low placental weight andlow infant birth weight.Conclusion: This report suggests that the pharmacological management of this patient couldpossibly account for the findings.IntroductionCholine is a nutrient that is a precursor of phosphatidyl-choline and the plasma concentrations of both nutrientsare controlled by endogenous synthesis and dietary intake[1]. Both are important for the efficient turnover of lipidsfrom the liver and blood. Choline is also important forthe control of plasma homocysteine concentration and isthe precursor of the neurotransmitter acetylcholine,which is important for the proper functioning of choliner-gic neurons peripherally and in the brain.Patients with bipolar affective disorder are effectivelymanaged with pharmacological intervention, such as lith-ium, haloperidol and benztropine, but studies on theinfluence of these drugs on plasma choline and phos-phatidylcholine concentrations are limited. There is evi-dence that lithium can decrease the plasma availability ofthese important cell components [2,3], but whether thistranslates into depletion in the brain supply remainsquestionable [4].Published: 20 February 2008Journal of Medical Case Reports 2008, 2:55 doi:10.1186/1752-1947-2-55Received: 11 October 2007Accepted: 20 February 2008This article is available from: http://www.jmedicalcasereports.com/content/2/1/55© 2008 Gossell-Williams et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 4(page number not for citation purposes)Journal of Medical Case Reports 2008, 2:55 http://www.jmedicalcasereports.com/content/2/1/55When women with bipolar affective disorder becomepregnant, pharmacological management is complicatedbecause of possible risks to the foetus from the use ofmedications. Lithium, for example is classified as a cate-gory D drug [5], that is, having the potential to cause foe-tal malformations, including foetal cardiacmalformations [6,7]. However in the case of pregnantpatients with affective disorder, the benefits of therapy canoutweigh the risks. We report on the pregnancy outcomesof a patient with bipolar affective disorder treated withmood stabilizers in the antenatal clinic of the UniversityHospital of the West Indies.Case presentationThe patient was a 25-year-old gravida 2, presenting to theantenatal clinic at 13 weeks gestational age. Medical his-tory indicated that the patient was diagnosed with bipolardisorder ten years prior to this pregnancy. She was effec-tively managed with lithium carbonate (500 mg b.i.d.),haloperidol (Haldol®5 mg b.i.d.) and benztropine(Cogentin®, 2 mg b.i.d.) prior to pregnancy and the regi-men was continued through the pregnancy. Plasma con-centrations of the prescribed medication were notassessed. At 12 weeks gestation, the patient described herappetite as good, with two full meals and three snacks perday. Her pregnancy booking BMI was 21.99 and plasmahaemoglobin (Hb) was normal (11.4 mg/dL). Her hae-moglobin phenotype status is AA and she was both HIVand VDRL negative. The patient also reported regular sup-plementation with multivitamins specific for pregnancy(Materna®). Her blood pressure was normal at the begin-ning of the pregnancy at 110/70 mmHg and remainednormal until about 36 weeks of gestation. The weight gainfrom 15 to 36 weeks of gestation was 6.9 Kg and her Hbremained in the normal range throughout the pregnancy.She then started to lose weight moving from 73.1 Kg at 36weeks (+ 5 days) to 71.4 Kg at 38 weeks (+ 5 days) andrecorded an elevation in blood pressure from week 37until week 38. Her blood studies at 37 weeks were all nor-mal (Table 1).She was admitted to the antenatal ward at 38 weeks + 5days and labour was induced, however due to failure toprogress, a caesarean section was performed with the birthof a male infant at 39 weeks. The infant's birth Apgarscores were good: 9 at one minute and 10 at 5 minutes.The infant's birth weight was 2500 g, which is below themean for a term baby in the Jamaican population [8].Both infant and mother were discharged after three daysand no follow-up data of either was collected.The patient in this study was taken from a pool of sixteenwomen who were followed through all three trimesters ofpregnancy. In order to make further assessment of infantoutcomes in this case, we selected other women from thelarger study that were similarly matched in gestation age,weight gain, blood pressure, haemoglobin status andinfant gestational age at birth (Table 2). The most distinc-tive differences between these other women and thispatient were the lower birth weight of the infant (30%less) and lower placental weight (42% less).We measured both fasting plasma phosphatidylcholineand choline through the three trimesters of pregnancy(Table 3). For this patient, comparison between the datafrom trimester 1 (week 10–13) to trimester 3 (week34–37) showed that plasma phosphatidylcholine concen-tration decreased by 22% during this period, while theplasma choline decreased by 38%. Comparison of theTable 2: Comparison of variables between the patient with bipolar affective disorder and control patients.Variable Bipolar patient. Means ± S.D. N = 3Age/yrs 25 29 ± 9Height/cm 173.5 164.8 ± 7.2BMI 22 26.8 ± 2.3Weight Gain/Kg 6.9 6.5 ± 1.013 weeks Systolic/mmHg 100 103 ± 1522 weeks Systolic/mmHg 100 120 ± 1036 weeks Systolic/mmHg 110 110 ± 1013 weeks Diastolic/mmHg 60 63 ± 622 weeks Diastolic/mmHg 60 73 ± 636 weeks Diastolic/mmHg 80 77 ± 151st trimester Hb (g/dl) 11.4 14.2 ± 3.72nd trimester Hb (g/dl) 11.4 11.4 ± 1.13rd trimester Hb (g/dl) 11.9 11.2 ± 0.3Parity 2 2 ± 2Gestational age (days) 272 273 ± 2Birth weight (g) 2500 3573 ± 133Placental weight (g) 350 607 ± 51Crown Heel length (cm) 51 48.5 ± 3.0Head Circumference (cm) 32 33.6 ± 0.7Ponderal index (g/cm3) 18.8 32 ± 7.1Head Circumference:length ratio62.7 69.5 ± 3.0Placenta: Birth weight ratio14 17 ± 0.8The patient with bipolar affective disorder had lower infant birth weight and lower placental weight, resulting in lower ponderal index and placenta:birthweight ratio.Table 1: Haematological indexes measured for bipolar affective disorder patientSodium 135 mmol/l Globulin 31 g/lPotassium 4.7 mmol/l Direct Bilirubin 7 umol/lUrea 1.9 mmol/l Total Bilirubin 22 umol/lCreatinine 33 umol/ml Alkaline Phosphotase 85 IU/lUric acid 0.18 mmol/l G.G.T. 7 IU/lTotal protein 63 mmol/l S.G.O.T. 31 IU/lAlbumin 32 g/l PT 13.8/12.6PTT 32.8/30.6Page 2 of 4(page number not for citation purposes)Journal of Medical Case Reports 2008, 2:55 http://www.jmedicalcasereports.com/content/2/1/55controls showed the expected increase in plasma cholineand phosphatidylcholine concentrations.ConclusionWe found that in the case of our patient, there was an unu-sually low placental weight and a low infant birth weightwhen compared with data recorded from three controlpatients and from previous studies of our population [8].These previous studies also recorded an association of lowbirth weight infants with low haemoglobin concentra-tions, especially during the first trimester. However, thiswas not a factor in this case, as the patient maintainednormal plasma concentrations of haemoglobin through-out the pregnancy.Low weight gain during pregnancy is another risk factorthat contributes to low infant birth weight [9]; however,the control patients that experienced similar weight gaindid not give birth to low birth weight infants. Althoughour comparisons are limited by the lack of dietary intakeinformation, previous reports have confirmed that moodstabilizers can contribute to low birth weight outcome[10].On further comparison of this patient with controls, itappeared that there was a decrease in plasma choline andphosphatidylcholine concentrations in this patient. Bothnutrients are especially important during pregnancy andare actively transported to the foetus [1,11]. The decreasesin plasma concentrations of these nutrients in our patientwere unexpected, as plasma concentrations of both areincreased during pregnancy [12,13], possibly to ensureadequate supply to the foetus. Phosphatidylcholine, forexample, supplies important long chain polyunsaturatedfatty acids, and deficiency of polyunsaturated fatty acidsto the foetus is a known risk factor for negative foetal out-comes such as low birth weight [14]. Furthermore, animalstudies have demonstrated that inadequate maternal sup-ply of these nutrients impairs cognitive and memory func-tions of pups and that dietary supplementation with thesenutrients during pregnancy can prevent these effects[1,15].Our data analysis was limited by the lack of informationon the actual amounts of choline and phosphatidylcho-line that were consumed by this patient during pregnancyand therefore whether inadequate dietary intake contrib-uted to the unexpected depletions. However, previouslydocumented evidence supports negative influences of atleast one of the drugs involved (lithium) on these nutri-ents. We therefore conclude that there is need for furtherstudies to clarify the causal associations between drugtherapy, maternal outcomes, foetal outcomes and theavailability of these nutrients in patients being treated forbipolar affective disorder. Whether benefits could bederived from dietary supplementation with choline andphosphatidylcholine should also be considered.Competing interestsThe author(s) declare that they have no competing inter-ests.Authors' contributionsSZ acted as principal investigator on the study and wasresponsible for the assessment of the maternal data. HFacted as obstetric/gynaecology consultant and assessedthe maternal outcomes. MG was the investigator respon-sible for the collection data and overall assessment. Allauthors have read and approved this manuscript.ConsentSigned written informed consent was received from allpatients reported in this paper allowing for publication ofthe data. A copy of the written consent is available forreview by the editor-in-chief of this journal.AcknowledgementsThe results reported are part of a larger study that was funded by grants from the National Institute of Health (Fogarty Fellowship grant; DK 55865). Support for this work was also provided by grants from the NIH to UNC Table 3: Plasma phosphatidylcholine and choline concentration.Bipolar patient Means ± S.D. N = 3PHOSPHATIDYLCHOLINE (nmoles/ml)10–13 weeks 2158.96 1573.24 ± 50.7319–23 weeks 2180.34 1769.70 ± 324.5934–37 weeks 1677.86 1716.11 ± 423.70FREE CHOLINE(nmoles/ml)10–13 weeks 11.17 8.94 ± 1.8119–23 weeks 7.62 8.77 ± 1.4834–37 weeks 6.89 10.99 ± 1.94The table shows the plasma concentrations of phospahtidylcholine and choline for trimester 1 (10–13 weeks gestation), trimester 2 (19–23 weeks gestation) and trimester 3 (34–37 weeks gestation) for bipolar and control patients. The patient with bipolar affective disorder showed depletion of both compounds rather than the expected increase.Page 3 of 4(page number not for citation purposes)Journal of Medical Case Reports 2008, 2:55 http://www.jmedicalcasereports.com/content/2/1/55Publish with BioMed Central   and  every scientist can read your work free of charge"BioMed Central will be the most significant development for disseminating the results of biomedical research in our lifetime."Sir Paul Nurse, Cancer Research UKYour research papers will be:available free of charge to the entire biomedical communitypeer reviewed and published immediately upon acceptancecited in PubMed and archived on PubMed Central yours — you keep the copyrightSubmit your manuscript here:http://www.biomedcentral.com/info/publishing_adv.aspBioMedcentralClinical Nutrition research Unit (DK56350), Fulbright visiting researcher grant and funds provided by Caribbean Health Research Council.References1. Zeisel SH: Choline: an essential nutrient for humans.  Nutr2000, 16(7–8):669-671.2. Haag M, Haag H, Eisenried F, Greil W: RBC-choline: changes bylithium and relation to prophylactic response.  Acta PsychiatrScand 1984, 70(4):389-99.3. Pleul O, Muller-Oerlinghausen B: Lithium therapy and the turn-over of phosphatidylcholine in human erythrocytes.  Eur J ClinPharmacol 1986, 31(4):457-62.4. Wu RH, O'Donnell T, Ulrich M, Asghar SJ, Hanstock CC, SilverstonePH: Brain choline concentrations may not be altered ineuthymic bipolar disorder patients chronically treated witheither lithium or sodium valproate.  Ann Gen Hosp Psychiatry2004, 3(1):13.5. Prescribing Medicines in Pregnancy   [http://www.tga.gov.au/docs/pdf/medpreg.pdf]6. Jablensky AV, Morgan V, Zubrick SR, Bower C, Yellachich LA: Preg-nancy, delivery, and neonatal complications in a populationcohort of women with schizophrenia and major affective dis-orders.  Am J Psychiatry 2005, 162(1):79-91.7. Mallinger AG, Hanin I, Stumpf RL, Mallinger J, Kopp U, Erstling C:Lithium treatment during pregnancy: a case study of eryth-rocyte choline content and lithium transport.  J Clin Psychiatry1983, 44(10):381-4.8. Thame M, Wilks RJ, McFarlane-Anderson N, Bennett FI, Forrester TE:Relationship between maternal nutritional status andinfant's weight and body proportions at birth.  Eur J Clin Nutr1997, 51:134-138.9. Ehrenberg HM, Dierker L, Milluzzi C, Mercer BM: Low maternalweight, failure to thrive in pregnancy, and adverse preg-nancy outcomes.  Am J Obstet Gynecol 2003, 189(6):1726-30.10. Patton SW, Misri S, Corral MR, Perry KF, Kuan AJ: Antipsychoticmedication during pregnancy and lactation in women withschizophrenia : evaluating the risk.  Can J Psychiatry 2002,47(10):959-65.11. Zeisel SH, Mar MH, Zhou ZW, da Costa KA: Pregnancy and lac-tation are associated with diminished concentrations ofcholine and its metabolites in rat liver.  J Nutr 1995,125:3049-3054.12. Ozarda Ilcol Y, Uncu G, Ulus IH: Free and phospholipid-boundcholine concentrations in serum during pregnancy, afterdelivery and in newborns.  Arch Physiol Biochem 2002,110:393-399.13. Postle A, Al M, Burdge G, Hornstra G: The composition of indi-vidual molecular species of plasma phosphatidylcholine inhuman pregnancy.  Early Hum Dev 1995, 43:47-58.14. Leaf AA, Leighfield MJ, Costeloe KL, Crawford MA: Long chain pol-yunsaturated fatty acids and fetal growth.  Early Hum Dev 1992,30(3):183-91.15. Albright CD, Mar MH, Craciunescu CN, Song J, Zeisel SH: Maternaldietary choline availability alters the balance of netrin-1 andDCC neuronal migration proteins in fetal mouse brain hip-pocampus.  Brain Res Dev Brain Res 2005, 159(2):149-54.Page 4 of 4(page number not for citation purposes)

BioMed CentralJournal of Medical Case Reports
ssOpen AcceCase report
Unexpected depletion in plasma choline and phosphatidylcholine 
concentrations in a pregnant woman with bipolar affective disorder 
being treated with lithuim, haloperidol and benztropine: a case 
report
Maxine Gossell-Williams*1, Horace Fletcher2 and Steven H Zeisel3
Address: 1Department of Basic Medical Sciences, University of the West Indies, Jamaica, 2Department of Obstetrics, Gynaecology and Child Health, 
University of The West Indies, Jamaica and 3Department of Nutrition, School of Public Health and School of Medicine University of North 
Carolina at Chapel Hill, NC 27599, USA
Email: Maxine Gossell-Williams* - maxine.gossell@uwimona.edu.jm; Horace Fletcher - horace.fletcher@uwimona.edu.jm; 
Steven H Zeisel - steven_zeisel@unc.edu
* Corresponding author    
Abstract
Introduction: Patients with bipolar affective disorder can be effectively managed with
pharmacological intervention. This case report describes a pregnant woman with a ten-year history
of bipolar affective disorder that was being treated with lithium, haloperidol and benztropine.
Case presentation: The patient had a normal pregnancy, but developed an elevated blood
pressure and started to lose weight at 36 weeks of gestation. During pregnancy, plasma
concentrations of choline and phosphatidylcholine are increased to meet the demands of the
foetus. However, our findings in this case included depletion of plasma choline and
phosphatidylcholine concentrations. Other unusual outcomes included low placental weight and
low infant birth weight.
Conclusion: This report suggests that the pharmacological management of this patient could
possibly account for the findings.
Introduction
Choline is a nutrient that is a precursor of phosphatidyl-
choline and the plasma concentrations of both nutrients
are controlled by endogenous synthesis and dietary intake
[1]. Both are important for the efficient turnover of lipids
from the liver and blood. Choline is also important for
the control of plasma homocysteine concentration and is
the precursor of the neurotransmitter acetylcholine,
which is important for the proper functioning of choliner-
gic neurons peripherally and in the brain.
Patients with bipolar affective disorder are effectively
managed with pharmacological intervention, such as lith-
ium, haloperidol and benztropine, but studies on the
influence of these drugs on plasma choline and phos-
phatidylcholine concentrations are limited. There is evi-
dence that lithium can decrease the plasma availability of
these important cell components [2,3], but whether this
translates into depletion in the brain supply remains
questionable [4].
Published: 20 February 2008
Journal of Medical Case Reports 2008, 2:55 doi:10.1186/1752-1947-2-55
Received: 11 October 2007
Accepted: 20 February 2008
This article is available from: http://www.jmedicalcasereports.com/content/2/1/55
© 2008 Gossell-Williams et al; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 4
(page number not for citation purposes)
Journal of Medical Case Reports 2008, 2:55 http://www.jmedicalcasereports.com/content/2/1/55When women with bipolar affective disorder become
pregnant, pharmacological management is complicated
because of possible risks to the foetus from the use of
medications. Lithium, for example is classified as a cate-
gory D drug [5], that is, having the potential to cause foe-
tal malformations, including foetal cardiac
malformations [6,7]. However in the case of pregnant
patients with affective disorder, the benefits of therapy can
outweigh the risks. We report on the pregnancy outcomes
of a patient with bipolar affective disorder treated with
mood stabilizers in the antenatal clinic of the University
Hospital of the West Indies.
Case presentation
The patient was a 25-year-old gravida 2, presenting to the
antenatal clinic at 13 weeks gestational age. Medical his-
tory indicated that the patient was diagnosed with bipolar
disorder ten years prior to this pregnancy. She was effec-
tively managed with lithium carbonate (500 mg b.i.d.),
haloperidol (Haldol®5 mg b.i.d.) and benztropine
(Cogentin®, 2 mg b.i.d.) prior to pregnancy and the regi-
men was continued through the pregnancy. Plasma con-
centrations of the prescribed medication were not
assessed. At 12 weeks gestation, the patient described her
appetite as good, with two full meals and three snacks per
day. Her pregnancy booking BMI was 21.99 and plasma
haemoglobin (Hb) was normal (11.4 mg/dL). Her hae-
moglobin phenotype status is AA and she was both HIV
and VDRL negative. The patient also reported regular sup-
plementation with multivitamins specific for pregnancy
(Materna®). Her blood pressure was normal at the begin-
ning of the pregnancy at 110/70 mmHg and remained
normal until about 36 weeks of gestation. The weight gain
from 15 to 36 weeks of gestation was 6.9 Kg and her Hb
remained in the normal range throughout the pregnancy.
She then started to lose weight moving from 73.1 Kg at 36
weeks (+ 5 days) to 71.4 Kg at 38 weeks (+ 5 days) and
recorded an elevation in blood pressure from week 37
until week 38. Her blood studies at 37 weeks were all nor-
mal (Table 1).
She was admitted to the antenatal ward at 38 weeks + 5
days and labour was induced, however due to failure to
progress, a caesarean section was performed with the birth
of a male infant at 39 weeks. The infant's birth Apgar
scores were good: 9 at one minute and 10 at 5 minutes.
The infant's birth weight was 2500 g, which is below the
mean for a term baby in the Jamaican population [8].
Both infant and mother were discharged after three days
and no follow-up data of either was collected.
The patient in this study was taken from a pool of sixteen
women who were followed through all three trimesters of
pregnancy. In order to make further assessment of infant
outcomes in this case, we selected other women from the
larger study that were similarly matched in gestation age,
weight gain, blood pressure, haemoglobin status and
infant gestational age at birth (Table 2). The most distinc-
tive differences between these other women and this
patient were the lower birth weight of the infant (30%
less) and lower placental weight (42% less).
We measured both fasting plasma phosphatidylcholine
and choline through the three trimesters of pregnancy
(Table 3). For this patient, comparison between the data
from trimester 1 (week 10–13) to trimester 3 (week
34–37) showed that plasma phosphatidylcholine concen-
tration decreased by 22% during this period, while the
plasma choline decreased by 38%. Comparison of the
Table 2: Comparison of variables between the patient with 
bipolar affective disorder and control patients.
Variable Bipolar patient. Means ± S.D. N = 3
Age/yrs 25 29 ± 9
Height/cm 173.5 164.8 ± 7.2
BMI 22 26.8 ± 2.3
Weight Gain/Kg 6.9 6.5 ± 1.0
13 weeks Systolic/mmHg 100 103 ± 15
22 weeks Systolic/mmHg 100 120 ± 10
36 weeks Systolic/mmHg 110 110 ± 10
13 weeks Diastolic/mmHg 60 63 ± 6
22 weeks Diastolic/mmHg 60 73 ± 6
36 weeks Diastolic/mmHg 80 77 ± 15
1st trimester Hb (g/dl) 11.4 14.2 ± 3.7
2nd trimester Hb (g/dl) 11.4 11.4 ± 1.1
3rd trimester Hb (g/dl) 11.9 11.2 ± 0.3
Parity 2 2 ± 2
Gestational age (days) 272 273 ± 2
Birth weight (g) 2500 3573 ± 133
Placental weight (g) 350 607 ± 51
Crown Heel length (cm) 51 48.5 ± 3.0
Head Circumference (cm) 32 33.6 ± 0.7
Ponderal index (g/cm3) 18.8 32 ± 7.1
Head 
Circumference:length 
ratio
62.7 69.5 ± 3.0
Placenta: Birth weight 
ratio
14 17 ± 0.8
The patient with bipolar affective disorder had lower infant birth 
weight and lower placental weight, resulting in lower ponderal index 
and placenta:birthweight ratio.
Table 1: Haematological indexes measured for bipolar affective 
disorder patient
Sodium 135 mmol/l Globulin 31 g/l
Potassium 4.7 mmol/l Direct Bilirubin 7 umol/l
Urea 1.9 mmol/l Total Bilirubin 22 umol/l
Creatinine 33 umol/ml Alkaline Phosphotase 85 IU/l
Uric acid 0.18 mmol/l G.G.T. 7 IU/l
Total protein 63 mmol/l S.G.O.T. 31 IU/l
Albumin 32 g/l PT 13.8/12.6
PTT 32.8/30.6Page 2 of 4
(page number not for citation purposes)
Journal of Medical Case Reports 2008, 2:55 http://www.jmedicalcasereports.com/content/2/1/55controls showed the expected increase in plasma choline
and phosphatidylcholine concentrations.
Conclusion
We found that in the case of our patient, there was an unu-
sually low placental weight and a low infant birth weight
when compared with data recorded from three control
patients and from previous studies of our population [8].
These previous studies also recorded an association of low
birth weight infants with low haemoglobin concentra-
tions, especially during the first trimester. However, this
was not a factor in this case, as the patient maintained
normal plasma concentrations of haemoglobin through-
out the pregnancy.
Low weight gain during pregnancy is another risk factor
that contributes to low infant birth weight [9]; however,
the control patients that experienced similar weight gain
did not give birth to low birth weight infants. Although
our comparisons are limited by the lack of dietary intake
information, previous reports have confirmed that mood
stabilizers can contribute to low birth weight outcome
[10].
On further comparison of this patient with controls, it
appeared that there was a decrease in plasma choline and
phosphatidylcholine concentrations in this patient. Both
nutrients are especially important during pregnancy and
are actively transported to the foetus [1,11]. The decreases
in plasma concentrations of these nutrients in our patient
were unexpected, as plasma concentrations of both are
increased during pregnancy [12,13], possibly to ensure
adequate supply to the foetus. Phosphatidylcholine, for
example, supplies important long chain polyunsaturated
fatty acids, and deficiency of polyunsaturated fatty acids
to the foetus is a known risk factor for negative foetal out-
comes such as low birth weight [14]. Furthermore, animal
studies have demonstrated that inadequate maternal sup-
ply of these nutrients impairs cognitive and memory func-
tions of pups and that dietary supplementation with these
nutrients during pregnancy can prevent these effects
[1,15].
Our data analysis was limited by the lack of information
on the actual amounts of choline and phosphatidylcho-
line that were consumed by this patient during pregnancy
and therefore whether inadequate dietary intake contrib-
uted to the unexpected depletions. However, previously
documented evidence supports negative influences of at
least one of the drugs involved (lithium) on these nutri-
ents. We therefore conclude that there is need for further
studies to clarify the causal associations between drug
therapy, maternal outcomes, foetal outcomes and the
availability of these nutrients in patients being treated for
bipolar affective disorder. Whether benefits could be
derived from dietary supplementation with choline and
phosphatidylcholine should also be considered.
Competing interests
The author(s) declare that they have no competing inter-
ests.
Authors' contributions
SZ acted as principal investigator on the study and was
responsible for the assessment of the maternal data. HF
acted as obstetric/gynaecology consultant and assessed
the maternal outcomes. MG was the investigator respon-
sible for the collection data and overall assessment. All
authors have read and approved this manuscript.
Consent
Signed written informed consent was received from all
patients reported in this paper allowing for publication of
the data. A copy of the written consent is available for
review by the editor-in-chief of this journal.
Acknowledgements
The results reported are part of a larger study that was funded by grants 
from the National Institute of Health (Fogarty Fellowship grant; DK 55865). 
Support for this work was also provided by grants from the NIH to UNC 
Table 3: Plasma phosphatidylcholine and choline concentration.
Bipolar patient Means ± S.D. N = 3
PHOSPHATIDYLCHOLINE (nmoles/ml)
10–13 weeks 2158.96 1573.24 ± 50.73
19–23 weeks 2180.34 1769.70 ± 324.59
34–37 weeks 1677.86 1716.11 ± 423.70
FREE CHOLINE(nmoles/ml)
10–13 weeks 11.17 8.94 ± 1.81
19–23 weeks 7.62 8.77 ± 1.48
34–37 weeks 6.89 10.99 ± 1.94
The table shows the plasma concentrations of phospahtidylcholine and choline for trimester 1 (10–13 weeks gestation), trimester 2 (19–23 weeks 
gestation) and trimester 3 (34–37 weeks gestation) for bipolar and control patients. The patient with bipolar affective disorder showed depletion of 
both compounds rather than the expected increase.Page 3 of 4
(page number not for citation purposes)
Journal of Medical Case Reports 2008, 2:55 http://www.jmedicalcasereports.com/content/2/1/55Publish with BioMed Central   and  every 
scientist can read your work free of charge
"BioMed Central will be the most significant development for 
disseminating the results of biomedical research in our lifetime."
Sir Paul Nurse, Cancer Research UK
Your research papers will be:
available free of charge to the entire biomedical community
peer reviewed and published immediately upon acceptance
cited in PubMed and archived on PubMed Central 
yours — you keep the copyright
Submit your manuscript here:
http://www.biomedcentral.com/info/publishing_adv.asp
BioMedcentral
Clinical Nutrition research Unit (DK56350), Fulbright visiting researcher 
grant and funds provided by Caribbean Health Research Council.
References
1. Zeisel SH: Choline: an essential nutrient for humans.  Nutr
2000, 16(7–8):669-671.
2. Haag M, Haag H, Eisenried F, Greil W: RBC-choline: changes by
lithium and relation to prophylactic response.  Acta Psychiatr
Scand 1984, 70(4):389-99.
3. Pleul O, Muller-Oerlinghausen B: Lithium therapy and the turn-
over of phosphatidylcholine in human erythrocytes.  Eur J Clin
Pharmacol 1986, 31(4):457-62.
4. Wu RH, O'Donnell T, Ulrich M, Asghar SJ, Hanstock CC, Silverstone
PH: Brain choline concentrations may not be altered in
euthymic bipolar disorder patients chronically treated with
either lithium or sodium valproate.  Ann Gen Hosp Psychiatry
2004, 3(1):13.
5. Prescribing Medicines in Pregnancy   [http://www.tga.gov.au/
docs/pdf/medpreg.pdf]
6. Jablensky AV, Morgan V, Zubrick SR, Bower C, Yellachich LA: Preg-
nancy, delivery, and neonatal complications in a population
cohort of women with schizophrenia and major affective dis-
orders.  Am J Psychiatry 2005, 162(1):79-91.
7. Mallinger AG, Hanin I, Stumpf RL, Mallinger J, Kopp U, Erstling C:
Lithium treatment during pregnancy: a case study of eryth-
rocyte choline content and lithium transport.  J Clin Psychiatry
1983, 44(10):381-4.
8. Thame M, Wilks RJ, McFarlane-Anderson N, Bennett FI, Forrester TE:
Relationship between maternal nutritional status and
infant's weight and body proportions at birth.  Eur J Clin Nutr
1997, 51:134-138.
9. Ehrenberg HM, Dierker L, Milluzzi C, Mercer BM: Low maternal
weight, failure to thrive in pregnancy, and adverse preg-
nancy outcomes.  Am J Obstet Gynecol 2003, 189(6):1726-30.
10. Patton SW, Misri S, Corral MR, Perry KF, Kuan AJ: Antipsychotic
medication during pregnancy and lactation in women with
schizophrenia : evaluating the risk.  Can J Psychiatry 2002,
47(10):959-65.
11. Zeisel SH, Mar MH, Zhou ZW, da Costa KA: Pregnancy and lac-
tation are associated with diminished concentrations of
choline and its metabolites in rat liver.  J Nutr 1995,
125:3049-3054.
12. Ozarda Ilcol Y, Uncu G, Ulus IH: Free and phospholipid-bound
choline concentrations in serum during pregnancy, after
delivery and in newborns.  Arch Physiol Biochem 2002,
110:393-399.
13. Postle A, Al M, Burdge G, Hornstra G: The composition of indi-
vidual molecular species of plasma phosphatidylcholine in
human pregnancy.  Early Hum Dev 1995, 43:47-58.
14. Leaf AA, Leighfield MJ, Costeloe KL, Crawford MA: Long chain pol-
yunsaturated fatty acids and fetal growth.  Early Hum Dev 1992,
30(3):183-91.
15. Albright CD, Mar MH, Craciunescu CN, Song J, Zeisel SH: Maternal
dietary choline availability alters the balance of netrin-1 and
DCC neuronal migration proteins in fetal mouse brain hip-
pocampus.  Brain Res Dev Brain Res 2005, 159(2):149-54.Page 4 of 4
(page number not for citation purposes)


AJ: Antipsychotic medication during pregnancy and lactation in women with schizophrenia : evaluating the risk.

and neonatal complications in a population cohort of women with schizophrenia and major affective disorders.

Choline: an essential nutrient for humans. Nutr

Erstling C: Lithium treatment during pregnancy: a case study of erythrocyte choline content and lithium transport. J Clin Psychiatry

Hornstra G: The composition of individual molecular species of plasma phosphatidylcholine in human pregnancy. Early Hum Dev

Lithium therapy and the turnover of phosphatidylcholine in human erythrocytes.

Low maternal weight, failure to thrive in pregnancy, and adverse pregnancy outcomes.

MA: Long chain polyunsaturated fatty acids and fetal growth. Early Hum Dev

PH: Brain choline concentrations may not be altered in euthymic bipolar disorder patients chronically treated with either lithium or sodium valproate. Ann Gen Hosp Psychiatry

Pregnancy and lactation are associated with diminished concentrations of choline and its metabolites in rat liver.

TE: Relationship between maternal nutritional status and infant's weight and body proportions at birth.

Ulus IH: Free and phospholipid-bound choline concentrations in serum during pregnancy, after delivery and in newborns. Arch Physiol Biochem

W: RBC-choline: changes by lithium and relation to prophylactic response. Acta Psychiatr Scand

Zeisel SH: Maternal dietary choline availability alters the balance of netrin-1 and DCC neuronal migration proteins in fetal mouse brain hippocampus. Brain Res Dev Brain Res

http://doaj.org/search?source=%7B%22query%22%3A%7B%22bool%22%3A%7B%22must%22%3A%5B%7B%22term%22%3A%7B%22id%22%3A%2272ac923eef0f44648ffe132e7193ccd2%22%7D%7D%5D%7D%7D%7D

Unexpected depletion in plasma choline and phosphatidylcholine concentrations in a pregnant woman with bipolar affective disorder being treated with lithuim, haloperidol and benztropine: a case report

Abstract

Similar works

Full text

Available Versions

Crossref

Springer - Publisher Connector

Directory of Open Access Journals

Carolina Digital Repository

Springer - Publisher Connector