Accepted Manuscript Nausea and vomiting in early pregnancy of adolescent: relationship with depressive symptoms Elif Yilmaz, M.D., Zehra Yilmaz, M.D., Bulent Cakmak, M.D., Assist. Prof., Mehmet Fatih Karsli, M.D., Ismail Burak Gultekin, M.D., Nihan Guneri Dogan, M.D., Osman Fadil Kara, M.D., Assoc. Prof., Tuncay Kucukozkan, M.D., Prof. PII:

S1083-3188(15)00259-4

DOI:

10.1016/j.jpag.2015.06.010

Reference:

PEDADO 1872

To appear in:

Journal of Pediatric and Adolescent Gynecology

Received Date: 11 February 2015 Revised Date:

16 June 2015

Accepted Date: 22 June 2015

Please cite this article as: Yilmaz E, Yilmaz Z, Cakmak B, Karsli MF, Gultekin IB, Guneri Dogan N, Kara OF, Kucukozkan T, Nausea and vomiting in early pregnancy of adolescent: relationship with depressive symptoms, Journal of Pediatric and Adolescent Gynecology (2015), doi: 10.1016/j.jpag.2015.06.010. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT Title: Nausea and vomiting in early pregnancy of adolescent: relationship with

Elif YILMAZ, M.D. 1 Zehra YILMAZ, M.D. 2 Bulent CAKMAK, M.D., Assist. Prof. 3

Ismail Burak GULTEKIN, M.D. 5 Nihan GUNERI DOGAN, M.D. 6

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Mehmet Fatih KARSLI, M.D. 4

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Author names and affiliations:

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depressive symptoms.

Osman Fadil KARA, M.D., Assoc. Prof. 7

1,2,4,5,6,7,8

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Tuncay KUCUKOZKAN, M.D., Prof. 8

Dr. Sami Ulus Women’s and Children’s Health Teaching and Research

Gaziosmanpasa University, School of Medicine, Department of Obstetrics and

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3

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Hospital, Department of Obstetrics and Gynecology, 06200, Sihhiye, Ankara, Turkey.

Gynecology, 60100, Merkez, Tokat, Turkey.

Institution where the actual work was done: Dr. Sami Ulus Women’s and Children’s Health Teaching and Research Hospital, Department of Obstetrics and Gynecology, 06200, Sihhiye, Ankara, Turkey.

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ACCEPTED MANUSCRIPT Corresponding Author:

Bulent Cakmak, Assist. Prof., M.D.

Gynecology, Sevki Erek Yerleskesi, 60100, Tokat, Turkey.

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E-mail: [email protected]

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Gaziosmanpasa University School of Medicine, Department of Obstetrics and

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Phone: +90 356 2125000/1064 Fax: +90 356 2122142

Sources of funding and acknowledgements: None.

Disclosure of potential conflicts: The authors (Elif Yilmaz, Zehra Yilmaz, Bulent Cakmak, Mehmet Fatih Karsli, Ismail Burak Gultekin, Nihan Guneri Dogan, Osman

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of interest.

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Fadil Kara, Tuncay Kucukozkan) have declared no financial disclosure and no conflict

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ACCEPTED MANUSCRIPT ABSTRACT STUDY OBJECTIVE: To determine the relationship between nausea and vomiting severity during pregnancy (NVP) and depressive symptoms in pregnant adolescent

DESIGN: Prospective cross-sectional study.

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females.

SETTING: A maternity research hospital outpatient clinic, Ankara, Turkey.

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PARTICIPANTS: A total of 200 pregnant adolescent females.

INTERVENTIONS AND MAIN OUTCOME MEASURES: Demographic features

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and obstetric histories of the participants were assessed. The Rhodes test was performed to determine nausea and vomiting severity in a face-to-face interview, and the selfreported Edinburgh Postnatal Depression Scale was administered under supervision. RESULTS: The Rhodes test results showed that 52 patients (26%) were classified with

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none, 83 (41.5%) with mild, 48 (24.0%) with moderate, or 17 (8.5%) with severe symptoms. The mean depression score in the severe vomiting group was significantly higher than that in the no NVP and mild NVP groups (p = 0.028 and 0.041,

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respectively). No difference was found between the other groups. CONCLUSION: Severe nausea-vomiting was associated with greater depressive

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symptom severity in pregnant adolescent females.

Key words: Adolescent, pregnancy, nausea, vomiting, depression.

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ACCEPTED MANUSCRIPT INTRODUCTION Nausea and vomiting during pregnancy (NVP) affects 70–80% of all pregnant females (1,2). In general, symptoms begin at weeks 4–6 of gestation, peak at 8–12 weeks, and

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resolve by weeks 16–20 (2,3). Approximately 20–30% of these individuals experience symptoms throughout pregnancy (4,5). Hyperemesis gravidarum (HG) (a severe form of NVP) is a condition of intractable vomiting during pregnancy, one of the most frequent

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causes of hospitalization during the first few months of pregnancy, and is characterized by dehydration, electrolyte and acid–base imbalance, nutritional deficiency, and weight

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loss (loss of > 5% of pre-pregnancy body weight) (6,7). Despite decades of research, the pathogenesis of NVP and HG remains unknown, but it is considered a multi-factorial condition. Although the hypothesis that endocrine factors (i.e., human chorionic gonadotropin) are the primary cause of HG, various biological, psychosocial, and

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socioeconomic factors have also been implicated in the pathogenesis (6,8).

It has been commonly believed that NVP has a psychological component, as HG is particularly common in patients with an underdeveloped personality, an unplanned

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pregnancy, advanced addiction, pregnancy-induced anxiety, or symptoms of hysteria,

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conversion, neurosis, or depression. However, HG has more recently been blamed as the cause for psychological symptoms due to the mental and physical stress associated with persistent nausea and vomiting, etc. (9). Depression is the most frequently observed psychological disorder during pregnancy and an important public health issue, as it affects fetal and maternal health, is an important risk factor for postpartum depression, may cause complications during pregnancy (hypertensive disorder/preterm birth), and results in unfavorable fetal characteristics (lower birth weight and lower Apgar score) and childhood (behavioral

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ACCEPTED MANUSCRIPT and emotional problems) problems (10-14). Although a relationship between NVP and antepartum depression has been shown in some studies (15,16), the role of NVP and its severity and the risk factors that could lead to antepartum depression in pregnant

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adolescent females who have NVP have received little attention. Adolescent pregnancy has increased, particularly in low- and middle-income countries, with an estimated 16 million adolescents aged 15–19 years giving birth each year (18). Adolescent pregnancy

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is associated with adverse obstetric and neonatal outcomes, such as anemia, preterm birth, pre-eclampsia, low birth weight, and small for gestational age (19,20). In this

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study, we determined the relationship between NVP severity and depressive symptoms in pregnant adolescent females with NVP.

MATERIALS AND METHODS

This cross-sectional study was conducted from September 2013 to May 2014 at the

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antenatal clinic of the Maternity and Women’s Health Training and Research Hospital, which is a major maternity hospital in Ankara, Turkey, a semi-urban region with low to middle socioeconomic demographics. The study population consisted of 200 pregnant

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adolescent females aged between 16 and 19 years, who were in viable singleton

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pregnancies without congenital malformations, and who attended the antenatal clinic during their first trimester for routine antenatal follow-ups. Patients with systemic disease (diabetes, thyroid dysfunction, acute urinary tract infection, or hepatobiliary or upper gastrointestinal system diseases) that could lead to nausea and vomiting, history of depression, threatened abortion, and patients with HG were excluded. This study was approved by the Ethics Committee, all females were informed about the study, and informed written consent was obtained, and written informed consent was obtained from parents when the participant was under 18. The presence of NVP was confirmed 5

ACCEPTED MANUSCRIPT by patient self-report and was classified according to severity using the Rhodes Test, as no NVP, mild NVP, moderate NVP, and severe NVP. Severe NVP is not HG. It was considered as HG when it had ketonuria, dehydration, electrolyte imbalance, nutrient

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depletion and the loss of at least 5% body weight, and HG was used as exclusion criteria in this study.

Gestational age was determined by obstetric ultrasonography. Urinalysis, kidney, liver,

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and thyroid function tests; and a complete blood count were conducted and recorded. The sociodemographic characteristics of the females were evaluated with a

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questionnaire containing questions, such as age, marital status, educational level, presence of health security, employment outside the house, educational level and employment of the husband, total monthly income, family structure (number of individuals living at home and their associations), whether the baby was planned, and

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the mental disorder history of the mother and her first-degree relatives. After completing the sociodemographic questionnaire and the Rhodes test during a face-toface interview, the females were administered the self-report Edinburgh Postnatal

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Depression Scale (EPDS) under supervision.

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The Rhodes test was developed by Rhodes et al. in 1984 to determine the severity of nausea and vomiting in patients receiving cancer chemotherapy, but the scale is often used for NVP (19-21). Patients were asked eight questions about their feelings of nausea, vomiting, and retching; the number, duration, and volume of vomit at any time; and their discomfort, with scores of 8–40. A score < 8 was considered no NVP, 9–18 mild, 19–32 moderate, and 33–40 severe NVP.

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ACCEPTED MANUSCRIPT Depressive symptoms were determined with the EPDS, which was developed by Cox et al. in 1987 (22). The EPDS is the most widely used screening tool to assess antepartum and postpartum depression, and its validity and reliability have been confirmed in many

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countries (23,24). The scale was adapted to Turkish by Engindeniz et al. in 1996. Its validity and reliability were demonstrated by the same group, and sensitivity and selectivity are 84.0% and 88.0%, respectively (25). The EPDS consists of 10 questions

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referring to depressive and dysphoric moods, loss of pleasure, sleep disorders, reduced performance, and thoughts of death, suicide, and guilt. Each item answer is assigned 0–

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3 points. Total scores are 0–30.

All data were analyzed using PASW statistics ver. 18.0 software (SPSS Inc., Chicago, IL, USA). Results are presented as means ± standard deviations and numbers (%). Analysis of variance with Dunnett’s post hoc test was used to detect differences

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between groups of parametric variables. The Kruskal–Wallis test was used to compare nonparametric variables. Differences between groups of categorical variables were assessed using the χ2 or Fisher’s exact test. Pearson’s correlation analysis was used to

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evaluate the associations between parametric variables. A p-value < 0.05 was

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considered to indicate significance.

RESULTS

Mean age of the 200 pregnant adolescent females was 17.4 ± 1.1 years (range, 15–19 years), and mean gestational age was 8.5 ± 2.3 weeks (range, 5–14 weeks). The Rhodes test results showed that 74% of the patients had NVP; 41.5% (n = 83) had mild, 24% (n = 48) had moderate, and 8.5% (n = 17) had severe symptoms, whereas 26% of the patients did not have NPV. No differences were found between the groups in the

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ACCEPTED MANUSCRIPT sociodemographic characteristics, such as age, number of gestational weeks, body mass index, educational level, income, depression history, smoking, or the other sociodemographic factors (Table 1).

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The lowest EPDS scores were found in the group with no NVP, and the highest scores were found in the severe NVP group (p = 0.008). The mean depression score in the severe NVP group was significantly higher than that in the no NVP and mild NVP

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groups (p = 0.028 and 0.041) (Figure 1). No difference was found between the other groups. The EPDS depression score was positively correlated with NVP severity

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(Pearson’s correlation coefficient = 0.268; p < 0.001).

DISCUSSION

NVP is the most common medical condition during pregnancy and is a major health

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problem for pregnant females and their families with physiological, emotional, social and economic consequences. Although many studies about NVP have been performed, the NVP frequency, risk factors, and outcomes in pregnant adolescent females have

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received limited attention. In our study, 74% of the patients had NVP of different severities. Consistent with our results, other studies have reported that up to 80% of all

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pregnant females experience some form of nausea and vomiting during pregnancy (1,2,26).

Maternal health can be adversely affected during pregnancy, and it can be a period filled with emotional and psychological problems, particularly in adolescent females (27). Although a psychological origin has been considered in pregnant females complaining of severe fatigue and NVP during early pregnancy and pregnancy-related stress,

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ACCEPTED MANUSCRIPT depression, and anxiety may be more significant findings in these patients, there is no consensus on exaggeration of these issues that may occur. Furthermore, the interactions among biological and psychological factors are unclear, because comparative tests were

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not performed. Sentimentalism, immature or histrionic personality, and age or cultural differences with a spouse are often present in these females (28). McCarty et al. reported that females with HG, particularly severe HG, are at increased risk for

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cognitive, behavioral, and emotional dysfunction during pregnancy (29).

Although it is unclear whether physiological symptoms are the cause or the result of

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NVP, and NVP, particularly HG, is seen most commonly in females with a psychological disorder, psychological disorders are currently considered the result of HG rather than the cause. Moreover, the stress and physical burden caused by NVP is the main reason for depression in these females (30-32). Therefore, NVP and HG are

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not the result of a conversion disorder or other psychological disorder but may cause physiological reactions that increase physical symptoms in pregnant females. Although the relationship between HG and psychiatric disorders has been examined, no consensus

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on this issue has been reached. Despite the few studies showing that HG is not a risk

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factor for antenatal depression or other psychosomatic disorders (33-34), the general view is that the risk for antenatal depression increases in females with NVP, particularly in severe cases, which is consistent with our results. King et al. examined 120 pregnant females and found significantly higher depression scores in those with HG than in a control group (35). Swallow et al. showed an association between NVP during early pregnancy and psychiatric morbidity; however, they did not detect a correlation between NVP severity and morbidity, as we found here (32). Poursharif et al. evaluated a large cohort of females with HG and reported that 80% have negative psychosocial changes

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ACCEPTED MANUSCRIPT and psychiatric sequelae consisting of depression and anxiety that continued postpartum in some cases (36). Kim et al. showed that pregnant females with HG report impaired health-related quality of life, and that a psychiatric consultation should be considered in

adolescent females with NVP are sparse.

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these individuals (37). Studies of the incidence of antepartum depression in pregnant

Pregnant adolescent females with severe NVP had a greater risk for antepartum

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depression in our study. The high depression rate in the severe NVP group in our study may have been due to inadequate food intake, chronic fatigue or insomnia, pregnancy-

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related ambivalence, or fear for the baby, based on poor nutrition or weight loss (38). As antepartum depression affects mental and physical health, it can reduce a mother’s self-care ability and increase the number of complications during pregnancy; therefore, it has a negative impact on the mother’s and baby’s health. Hypertensive diseases

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occurring during pregnancy (pre-eclampsia/eclampsia), preterm labor, small for gestational age, low birth weight, and low Apgar scores in newborns are among the most important factors associated with depression during pregnancy (9,11,39). Babies

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born to such mothers have a higher probability of developing future behavioral and

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emotional problems (40). In addition, antepartum depression is one of the most important risk factors for postpartum depression, as approximately 50% of females who suffer from depression during pregnancy also suffer from postnatal depression (40,41).

The limitations of this study are its cross-sectional nature, the small number of participants, and the use of the EPDS as a diagnostic tool. This study would be more strength, if it was longitudinal study with large population. Depressive symptoms could be evaluated at advanced gestational week and postpartum period. On the other hand,

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ACCEPTED MANUSCRIPT any other tests could be used for assessment of depression and / or anxiety. Thus, larger prospective studies are needed to clarify the role of NVP in depression during the antepartum period.

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In conclusion, as untreated depression during adolescent pregnancy is a serious public health problem that can lead to many complications affecting the mother and fetus, it is important to recognize antepartum depression in pregnant adolescent females with NVP.

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Our findings suggest that pregnant adolescent females with severe NVP have a greater risk for antepartum depression. Therefore, the psychological profile of these patients

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must be seriously considered, and patients with serious NVP should be given psychological support as well as medical treatment.

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ACCEPTED MANUSCRIPT 16. Koken G, Yilmazer M, Cosar E, Sahin FK, Cevrioglu S, Gecici O. Nausea and vomiting in early pregnancy: Relationship with anxiety and depression. J Psychosom Obstet Gynaecol. 2008; 29:91-5.

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24. Adewuya AO, Ola BA, Dada AO, Fasoto OO. Validation of the Edinburgh Postnatal Depression Scale as a screening tool for depression in late pregnancy among Nigerian women. J Psychosom Obstet Gynaecol 2006; 27:267-72.

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ACCEPTED MANUSCRIPT 25. Engindeniz A, Küey L, Kültür S. Validity and reliability of Turkish form of Edinburgh Postpartum Depression Scale. Bahar Sempozyumları. Kitabı. 1996: 51-2. 26. Gadsby R, Barnie-Adshead Am, Jagger C. A prospective study of nausea and

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vomiting durind pregnancy. Br J Gen Pract 1993; 43:245-8. 27. Chen H, Chan YH, Tan KH, Lee T. Depressive symptomatology in pregnancy. Soc Psychiatry Psychiatr Epidemiol 2004; 39:975-9.

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28. Quinla JD, Hill DA. Nausea and vomiting of pregnancy. Am Fam 2003; 68:121-8. 29. McCarthy FP, Khashan AS, et al. A prospective cohort study investigating

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associations between hyperemesis gravidarum and cognitive, behavioural and emotional well-being in pregnancy. PLoS ONE 2011; 6:e27678. 30. Lee NM, Saha S. Nausea and vomiting of pregnancy. Gazstroenterol Clin North Am 2011; 40:309-34.

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31. Munch S. Chicken or the egg? The biological-psychological controversy surrounding hyperemesis gravidarum. Soc Sci Med 2002; 55:1267-78. 32. Swallow BL, Lindow SW, Masson EA, Hay DM. Psychological health in early

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pregnancy: Relationship with nausea and vomiting. J Obstet Gynaecol 2004; 24:28-

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33. Simpson SW, Godwin TM, Robins SB, et al. Psychological factors and hyperemesis gravidarum. J Women's Health Gend Based Med 2001; 10:471-7.

34. D'Orazio LM, Meyerowitz BE, Korst LM, et al. Evidence against a link between hyperemesis gravidarum and personality characteristics from an ethnically diverse sample of pregnant women: a pilot study. J Women's Health (Larchmt) 2011; 20:137-44.

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ACCEPTED MANUSCRIPT 35. King NM, Chambers J, O’Donnell K, et al. Anxiety, depression and saliva cortisol in women with a medical disorder during pregnancy. Arch Womens Ment Health 2010; 13:339-45.

gravidarum. J Perinatol 2008; 28:176-81.

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36. Poursharif B, Korst LM, Fejzo MS, et al. The psychosocial burden of hyperemesis

37. Kim DR, Connolly KR, Cristancho P, et al. Psychiatric consultation of patients with

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hyperemesis gravidarum. Arch Womens Ment Health 2009; 12:61-7.

38. Simsek Y, Celik O, Yilmaz E, et al. Assessment of anxiety and depression levels of

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pregnant women with hyperemesis gravidarum in a case-control study. J TurkishGerman Gynecol Assoc 2012; 13:32-6

39. Diego MA, Field T, Hernandez-reif M, et al. Prenatal depression restricts fetal growth. Early Hum Dev 2009; 85:65-70.

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40. Beck CT. The effects of postpartum depression on child development: a metaanalysis. Arch Psychiatr Nurs 1998; 12:12-20. 41. Beck CT. Predictors of postpartum depression: an update. Nurs Res 2001; 50:275-

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85.

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ACCEPTED MANUSCRIPT FIGURE LEGENDS Figure 1: Comparison of the Edinburgh Postnatal Depression Scale (EPDS) scores

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between the groups.

Numbers in the columns indicate the EPDS score for each group. The p-values were obtained by comparing the severe NVP group with the other groups. No differences were observed among the other three groups. NVP, nausea and vomiting during

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pregnancy.

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ACCEPTED MANUSCRIPT Table 1: Distribution of the socio-demographic characteristics of the groups

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Owner of Residence Owned Rented Voluntary Marriage Yes No Planned Pregnancy Yes No Depression history in first degree relatives Yes No Smoking Yes No

Severe NVP (n=17) 17.2±1.3 8.5±2.5 1.2±0.4 3.3±1.3 1.4±0.7 23.0±3.1

p 0.881 0.993 0.555 0.996 0.984 0.783

35(41.7) 30(41.1) 18(41.9)

20(23.8) 18(24.7) 10(23.3)

7(8.3) 6(8.2) 4(9.3)

23(31.5) 29(22.8)

32(43.8) 51(40.2)

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NVP degree Mild NVP Moderate NVP (n=83) (n=48) 17.4±1.2 17.5±1.1 8.5±2.3 8.5±2.2 1.5±1.0 1.4±0.6 3.3±1.4 3.2±1.3 1.4±0.6 1.4±0.6 23.2±2.4 22.7±3.3

22(26.2) 19(26.0) 11(25.6)

4(9.3) 13(10.2)

0.279

0.993

14(19.2) 34(26.8)

0.907

39(26.2) 13(25.5)

61(40.9) 22(43.1)

36(24.2) 12(23.5)

13(8.7) 4(7.8)

16(25.4) 26(26.0) 10(27.0)

27(42.9) 41(41.0) 15(40.5)

15(23.8) 24(24.0) 9(24.3)

5(7.9) 9(9.0) 3(8.1)

7(23.3) 45(26.5)

13(43.3) 70(41.2)

7(23.3) 41(24.1)

3(10.0) 14(8.2)

0.973

28(25.9) 24(26.1)

45(41.7) 38(41.3)

26(24.1) 22(23.9)

9(8.3) 8(8.7)

0.975

34(25.8) 18(26.5)

55(41.7) 28(41.2)

32(24.2) 16(23.5)

11(8.3) 6(8.8)

0.998

35(27.6) 17(23.3)

57(44.9) 26(35.6)

26(20.5) 22(30.1)

9(7.1) 8(11.0)

0.272

9(25.0) 43(26.2)

15(41.7) 68(41.5)

9(25.0) 39(23.8)

3(8.3) 14(8.5)

0.998

6(26.1) 46(26.0)

9(39.1) 74(41.8)

6(26.1) 42(23.7)

2(8.7) 15(8.5)

0.994

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Age Gestational week Duration of marriage Number of individuals living at home Association of individuals at home BMI Education Level Elementary school or lower High school University Employment Status Employed Unemployed Health Insurance Yes No Education Level of Spouse Elementary school or lower High school University Employment Status of Spouse Employed Unemployed

No NVP (n=52) 17.4±1.0 8.6±2.4 1.5±0.6 3.3±1.1 1.4±0.6 23.1±2.2

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Characteristics

0.991

First six parameters are given as mean±SD, other parameters as n(%). BMI: Body mass index, NVP: Nausea and vomiting of pregnancy.

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16 14

p=0.041

p=0.028

p=0.273

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12 10 8

4

8.7±3.4

8.9±3.8

No NVP

Mild NVP

9.8±4.5

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2

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0

12.2±4.2

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6

Moderate NVP

Severe NVP