EFFECT OF MULTIPARITY ON SEROTONIN AND OXYTOCIN HORMONES COMPARED TO PRIMIPARITY AND NULLIPARITY IN PREGNANT SUDANESE WOMEN.
In medicine, parity is the number of times a female has been pregnant and carried the pregnancies to a viable gestational age.  A woman who has given birth two or more times is called a multipara; while grand multipara describes the condition of having given birth five or more.  Grand multiparity has been considered an independent factor for increasing adverse outcome for both fetus and mother specially diabetes mellitus, antepartum haemorrhage, mal-presentation, caesarean section rate, postpartum haemorrhage, iron deficiency anaemia, and a high perinatal mortality rate.  More recent reports, however, have demonstrated that in the presence of good perinatal care, grand multiparity no longer need to be considered an obstetrical risk in the presence of satisfactory health care conditions. 
The majority of the studies argued that grand multiparas are more likely to be of old age which might be the reasons for increased morbidity and mortality. Such factor is difficult to be removed clinically because women's age is the most important biological variable that influences the reproductive health issue.  A few previous studies have shown that maternal grand multiparity may predict an increased risk of psychopathology in adult offspring. [6-7] These studies have shown that offspring born as a fourth or later born-child have higher risks of psychiatric hospitalizations for any reason, and that offspring born as a third or later-born child have an increased risk of personality and behavioural disorders in adult life . However, it remains unknown if the risks associated with maternal grand multiparity for mental disorders in the offspring persist after the transition into adulthood and to a more independent role in the society. It is also uncertain if maternal grand multiparity is independently associated with the risk of mental disorders or whether the associations found are confounded by maternal age at childbirth. 
In most cases, the changes in women's metabolism during pregnancy are a good thing they ensure a balance of health for both mother and fetus. But unfortunately in a recent study, almost all pregnant women have been noted to have changes in oxytocin and serotonin levels, overwhelmingly leading to abrupt and frequent changes in emotional state. 
Serotonin hormone or 5-hydroxytryptamine (5-HT) is fundamentally neurochemical molecule in brain cells, or neurons, when released makes human feel good when having something beneficial for survival. There is no evidence that serotonin directly underpins happiness. Over the past few decades, researchers have been discussing that mental health issues such as depression and anxiety might fundamentally be disorders of learning, rather than outcomes of a 'chemical imbalance' that requires correction by serotonin boost.  Whereas, oxytocin secreted from the pituitary gland cannot re-enter the brain because of the blood-brain barrier. Instead, the behavioural effects of oxytocin are thought to reflect release from centrally projecting oxytocin neurons, different from those that project to the pituitary gland.  Some popular media have labelled it the "love hormone," because it has sophisticatedly association with good feelings and emotions. It does appear to be connected to human emotions.  According to recent research, this hormone "is now believed to be involved in a wide variety of physiological and pathological functions such as maternal behaviour. 
And therefore, the aim of this study was to estimate effect of multiparity pregnant on serotonin and oxytocin hormones compared to primiparity and nulliparity in Sudanese women.
MATERIALS AND METHODS
This study was designed to be a comparative cross sectional study, this study was conducted in Khartoum State, Jabal Awlia Hospital, and Omdurman Maternity Hospital. The study was carried out during the period from September 2016 to April 2019. Three hundred women were enrolled in this study; 100 were multiparity pregnant women as study group, 100 were primiparity pregnant women as control positive group and 100 were nulliparity (Non-pregnant women) were the control negative group. The sampling technique used was convenience sampling. All participants were in their fertility period and/or premenopausal period, in age of 20-48 years old. Women were grouped into three groups comprising multiparity, primiparity and nulliparity. Questionnaires were administered. The demographic data like name, age, parity, gestational age, height, tall and BMI. Blood samples were collected via vein puncture in early morning (8:00-11:00 am). After centrifugation of blood sample, the sera were analysed for serotonin and oxytocin hormones levels by using
full-automated ELISA. All pregnant women were at 26-34 weeks gestational age. Since the duration of the study was less. The women were selected by convenience sampling technique. The sample size required was taken for convenience.
This study was approved by the research committee - College of Medical Laboratory Sciences-Shandi University. Informed consent was obtained from each participant before taking the samples.
Methods of BMI Estimation
It calculates a value indicative of the fat content of the body by dividing the weight by the square of height 
BMI = mass(kg)/[(height(m)).sup.2]
All pregnant women take drugs that have effect on estimation and/or with major hormonal disorder along with those refused to participate in this study were excluded.
Venous blood was collected using antiseptic for the skin, as well as data concerning any sample from clinical chemistry laboratories according to Inclusion criteria and exclusion criteria. Seven ml venous blood samples were obtained from each female using standard venipuncture technique  in serum separator tubes (SST). After 15 minutes, serum specimens were collected in plane container after centrifugation at 3000 rpm for 5 minutes. The serum stored frozen (-20[degrees]C) in a tightly sealed tube for only 2 weeks and then analyzed. Specimens should be allowed to come to room temperature and then mixed thoroughly by gentle inversion before assaying. Then serotonin and oxytocin were measured by automated Enzyme-Linked Immunosorbent Assay (ELISA) kit.
Quality Controls and Managements
Blood was collected with care and adequate safety precautions to ensure test results were reliable. Quality Assurance (QA) and standard Operating System was followed for all biological and clinical tests to achieve validity and reliability of test results.
All data are presented as mean [+ or -] SD. Statistical significance was determined using one-way ANOVA followed by Tukey's multiple comparison test. In results with only two set of data, unpaired student's test with Welch correction (Unequal sample size) was used. Though the SD values were high in some parameters, ANOVA was used as it has been reported to be robust for different types of data. 
Table 1, Figure 1, Figure 2 shows the statistics of demographic data and biochemical parameters computed for the three groups (Nulliparity, Primiparity and Multiparity). The results showed that there is statistical significance difference between the groups means for all parameters respectively.
Table 2. There was a weak positive correlation between oxytocin and age among multiparous women. This correlation was found to be statistically significant.
The pregnancy is associated with many physiological and morphological changes to suit the needs of the growing fetus. These changes accompanying pregnancy are feared to have deleterious effects for mother and baby as the number of gestations.
In the present study, the results revealed that the mean concentration of the serotonin and oxytocin in multiparity pregnant women were significantly altered as compared to nulliparity women as well as primiparity pregnant women (p value<0.001).
Previous studies had further expands on this pattern, by reporting strong and significant rank-order correlations for within-subject oxytocin levels for all three time-periods, covering a 6 month epoch and spanning two distinct phases, pregnancy and the early post partum. 
In the present study the results showed that for age there is statistical significance difference between the groups means for all parameters (P= < 0.001), for BMI and serotonin in there no statistical significance difference between multiparity and nulliparity respectively. Also, for oxytocin there is no statistical significance difference primiparity and nulliparity.
In the present study the correlation of oxytocin and serotonin means with age and BMI within the three groups. The results showed that for multiparity there is statistical significance difference between (age and oxytocin P=0.002).
Previous studies concluded that significant age-related changes in the female hormonal environment occur during the reproductive years. 
Nevertheless, previous studies were showed that multiparity is a risk factor for obesity in later life either before or after menopause and definitely real association between the number of parities and obesity was noticed. 
Levels of oxytocin hormones are significantly affected by multiparty and the age of pregnant women.
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Mutasem Mahmoud Abdallah Ahmed (1), Kamal Ahmed Abdelsalam (2), Mutaz Ibrahim Hassan (3)
(1) Wepartment of Clinical Chemistry, Faculty of Medical Laboratory Sciences-Shendi University, Sudan.
(2) Department of Clinical Laboratory Sciences, Applied Medical College, Shaqra University.
(3) Department of Clinical Chemistry, Faculty of Medical Laboratory Sciences-Shendi University, Sudan.
'Financial or Other Competing Interest': None.
Submission 27-09-2018, Peer Review 08-02-2019, Acceptance 15-02-2019, Published 25-02-2019.
Mutasem Mahmoud Abdallah Ahmed, Khartoum-Sudan.
Department of Clinical Chemistry, Faculty of Medical Laboratory Sciences-Shendi University, Sudan.
Caption: Figure 1. Comparison of Serotonin Hormone Within Groups
Caption: Figure 2. Comparison of Oxytocin Hormone Within Groups
Caption: Figure 3. Correlation Between Oxytocin Hormone and Age in Multiparity Group
BMI Categories Categories BMI Under Weight Less Than 18.5 Normal Weight 18.5-24.9 Over Weight 25-29.9 Obese 30 or Higher Table 1. Statistics of Demographic Data and Biochemical Parameters Parameters Nulliparity Primiparity Serotonin 236 [+ or -] 103 85.4 [+ or -] 71 *** Oxytocin 236 [+ or -] 288 356 [+ or -] 369 *** BMI 23.5 [+ or -] 1.5 28.0 [+ or -] 3.15 * Age 32.1 [+ or -] 2.7 25.5 [+ or -] 3.6 ** Parameters Multiparity Serotonin 96 [+ or -] 66 *** (aaa) Oxytocin 783 [+ or -] 1126.8 *** (aaa) BMI 28.0 [+ or -] 3.5 * Age 30.2 [+ or -] 4.0 *** (aaa) Age values are mean [+ or -] SD, Serotonin, Oxytocin hormones and BMI value are Median [+ or -] IQR * P<0.05, ** P<0.01, *** P<0.001 compared to nulliparity, (aaa) P<0.001 compared to primiparity Table 2. Spearman Correlation Coefficient (R) Between Demographic Data and Biochemical Parameters Within Groups Parameters Multiparity Primiparity Nulliparity r p r p r p Value Value Value Age-Serotonin 0.101 0.153 0.022- 0.829 0.035 0.728 Age-Oxytocin 0.220 0.002 -0.041 0.689 -0.129 0.200 BMI-Serotonin 0.041 0.565 0.053 0.597 -0.094 0.352 BMI--Oxytocin -0.003 0.964 -0.093 0.356 -0.001 0.992
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|Title Annotation:||Original Research Article|
|Author:||Ahmed, Mutasem Mahmoud Abdallah; Abdelsalam, Kamal Ahmed; Hassan, Mutaz Ibrahim|
|Publication:||Journal of Evolution of Medical and Dental Sciences|
|Date:||Feb 25, 2019|
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