Pregnancy is essentially a physiological process, which involves a great number of physiological changes, affecting virtually all the organ systems in the body. By the end of the first 12 to 14 weeks, most of these changes would have reached an appreciable magnitude. Indeed, it is believed that most of these changes are initiated in the luteal phase of every ovulatory menstrual cycle; the formation of corpus luteum of pregnancy only accentuates the situation (Chapman et al, .1997). Thus, the menstrual cycle functions, not just to produce fresh eggs each month, but also acts proactively to prepare the body for pregnancy.
The changes in ventilatory function during pregnancy may be unrelated to the obvious anatomical changes, which occur because of upward displacement by the gravid uterus. The sub-costal angle increases progressively from 68 degrees in early pregnancy to 103 degrees in late pregnancy and returns to normal within a few weeks of delivery (Thomas et al., 1938).Furthermore, it has been noted that the transverse diameter of the chest wall increases by about 2cm while the diaphragm is raised by about 4cm (Thomas et al., 1938, McGinty 1938). However, the total lung capacity decreases only slightly because of compensatory increase in the transverse and antero-posterior diameters of the chest, as well as flaring of the ribs (Broughton-Pipkin 2007). In the respiratory tract, hormonal changes stimulate the mucosal vasculature leading to capillary engorgement and swelling of the lining of the nose, oropharynx, larynx, and trachea. Airway resistance is reduced, causing increased ventilation and decreased partial pressure of CO2. This may probably be due to the progesterone-mediated loosening of ligaments and relaxation of the bronchial musculature. (Lyons and Anthonio 1959).
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Despite the upward displacement, the diaphragm moves with greater excursions during breathing in the pregnant than in the non-pregnant state. In fact, breathing is more diaphragmatic than thoracic during gestation; an advantage during supine positioning and high regional blockade (Lyons and Anthonio 1959). From the middle of the second trimester, expiratory reserve volume, residual volume and functional residual capacity are progressively decreased, by approximately 20% at term (Berry and McMurray 1989, Sroczynski 2002, McAuliffe et al., 2004). Lung compliance is relatively unaffected, but chest wall compliance is reduced, especially in the lithotomy position. A progressive increase in minute ventilation starts soon after conception and peaks at 50% above normal levels around the second trimester. This increase is effected by a 40% rise in tidal volume and a 15% rise in respiratory rate (Lyons and Anthonio 1959, Liberatore et al., 1984). Since dead space remains unchanged, alveolar ventilation is about 70% higher at the end of gestation. The increased ventilation decreases arterial and alveolar carbon dioxide tensions. An average paCO2 of 32 mmHg (4.3 kPa) and arterial oxygen tension of 105 mmHg (13.7 kPa) persist during most of gestation (Lyons and Anthonio 1959).These changes have far reaching clinical implications, as prior knowledge will assist greatly in the management of pregnant women with respiratory disorders. Furthermore, normal pregnant women also undergo significant changes in ventilatory function during spinal anaesthesia (Lyons and Anthonio 1959, Kelly et al., 1996).
This study, thus, aims at generally and specifically evaluating some ventilatory function changes as they affect normal pregnant women in our environment. Respiratory changes in pregnancy are of clinical importance to the anaesthetist, during administration of anaesthesia to pregnant women especially during childbirth and specifically during caesarean section. This study will assist in getting baseline values in all the trimesters of pregnancy, to enable accurate interpretation of spirometric values in the management of obstructive or restrictive lung diseases during pregnancy.
3.1 Study Area
The study is a descriptive cross sectional study carried out at the antenatal and booking clinics of the University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla and Kenechukwu specialist hospital Enugu and Chukwuasokam maternity hospital in Emene between April and July 2010.
3.2 Ethical Clearance
Ethical clearance was obtained from the ethical committee of the UNTH, Enugu.
3.3 Sampling Size and Sampling Technique;
To calculate the minimum sample size for comparing the means of FVC, FEV1, PEFR, and, FVC/FEV1 and their various percentage predicted values among the groups, the following formula was used (Campbell and Machin 1996):
n = 2 (Zα + Z )2 Æ¡ 2
where n = minimum sample size in each group
Zα = % point of the normal distribution corresponding to the one - sided significance level (e.g. if significance level is 5%, then Zα = 1.65)
Always on Time
Marked to Standard
Z = one sided percentage point of the normal distribution; corresponding to the power. If the power is 80% then Z = 0.84.
σ = Population Standard deviation
δ = m2 - m1 = expected difference in means
From, previous studies the expected mean differences ranges from 5% to 10 %. For FVC, FEV1, PEFR, and ERV; the average population standard deviation is about ± 0.76 and the average mean difference is about 0.56
Therefore n = 2(1.65 + 0.84)2 x 0.762
= 12.4002 x 0.58 = 23
For the percentage predicted values, the average population standard deviation is about ± 15 while the average mean difference is about 10.
n = 2(1.65 + 0.84)2 x 152
= 12.4002 x 225 = 28
Thus, the minimal sample size for this study is about 28 for each group making 112. However, we recruited 200 pregnant women and 100 non-pregnant by systematic random sampling. This was to take care of those who will not complete the rigorous processes involved in standard spirometry.
3.4 Inclusion Criteria
All confirmed pregnant women who do not have any of the exclusion criteria.
Willingness to participate.
Ability to demonstrate sufficient proficiency in carrying out the tests needed to assess ventilatory function.
3.5. Exclusion Criteria
Patients with the following will be excluded:
Pre existing cardio-respiratory diseases like asthma, Chronic Obstructive
Airway Disease (COPD), Congestive Cardiac Failure (CCF).
Presence of spinal deformities (scoliosis, kyphoscoliosis)
Upper and lower respiratory tract infections.
Medications that alter lung function (e.g. bronchodilators and constrictors).
Acute malaria in pregnancy.
Diabetes in pregnancy.
Other pregnancy complications (threatened abortion, antepartum haemorrhage etc).
HIV positive patients.
Subjects who had worked or who work in dusty environments like coal mining or street sweepers.
Others include febrile conditions, multiple pregnancy, chronic renal disease, sickle cell anaemia.
For optimal and repeatable results to be obtained, the following was avoided;
Consuming alcohol within four hrs of testing.
Vigorous exercise within 30 minutes of testing.
Wearing clothes that substantially restrict chest and abdominal movement
Eating large meal within two hours of testing.
Chest or abdominal pain of any aetiology.
Pain in the mouth or face that will be worsened by mouthpiece, dementia or confusional state and stress incontinence (Miller et al,.2004).
These were clearly explained to these subjects during counseling in the booking clinic. Those who met the criteria were tested immediately while the rests were followed up later to their respective antenatal clinics.
3.6 Control Population
They were recruited from normal non-pregnant female staff of the UNTH Enugu, who met the inclusion criteria for the pregnant subjects. These subjects were matched for age, and height. Pregnancy was be ruled out by performing the test on the 7th day of the last normal menstrual period and performing pregnancy test using early morning urine.
3.7 Recruitment of Study Subjects
Subjects were recruited by systematic random sampling of all the women at various trimesters that were resident in Enugu state and attending the antenatal clinic. The method of recruitment was also same for the non-pregnant control subjects. One out of every two patients attending the ANC was recruited by simple random sampling using a lucky dip of yes or no. Verbal informed consent was also obtained from the patients. After obtaining ethical clearance and informed consent, about 300 patients who meet the above criteria were recruited.
A pre-tested questionnaire patterned after the 1976 British MRC questionnaire on respiratory symptoms, as modified by Pistelli et al. (2001) was used. Some house officers were trained on the administration of the questionnaire and they obtained obtain the information directly from the subjects. These include, general information, familial diseases, general diseases, respiratory diseases, respiratory symptoms, allergic symptoms ,active smoking, passive smoking, occupational history, environmental conditions, social and economic conditions, diet, physical activity, daily activity pattern, use of respiratory medicines, use of health services, health status and quality .
English language combined with vernacular where necessary was used by the investigator in administering the questionnaire. The following history were obtained from the subjects; personal history, history of present pregnancy, past obstetric history, past medical history, family and social history and review of systems. The gestational age was assessed from the last normal menstrual period. Only those who were sure of their last menstrual period were included. Trimester was defined as first trimester (< 14 weeks), second (14 weeks - 27 weeks) and third (> 27weeks). Clinical and obstetric examinations were performed. Axillary temperature was taken to exclude fever and temperature of less than 37.5oc was considered as normal.
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The following anthropometric measurements were performed;
Weight was measured to the nearest 0.5 kilogram using a standard weighing scale (STADIOMETER, SECA, MODEL 220, GERMANY).
The height was measured in meters, without shoes, with the feet together, standing as tall as possible with the eyes level and looking straight ahead. Measurement was done to the nearest centimeter using a standard measuring stick. (STADIOMETER, SECA, MODEL 220, GERMANY).
All the subjects and controls were subjected to the same instrument and method of measurement.
Body mass index was calculated by dividing the weight in Kg with the square of the height in meters and expressed as Kg/m2. The mid-upper arm circumference (MUAC), which is the circumference of the upper arm at that same midpoint, was measured in centimetres with a non-stretchable tape measure. The waist circumference was measured by locating the iliac crest and thereafter applying a tape above it asking the participant to wrap it round them. The tape was checked to make sure it was horizontal across the back and front of the subjects. The hip circumference was measured by positioning the measuring tape around the maximum circumference of the buttocks at the level of the groin (NHANES III).
3.9 Equipment and Procedure
The ambient temperature was measured on each day. The respiratory rate was also measured. A standard Spirometer (Micro lab ML3500 MK8, Cardinal Health Germany 234 GMBH) with disposable mouth piece was used throughout the study to determine some forced ventilatory functions (FEV1, FVC, FVC/FEV1, and PEFR ).This involve general and where necessary individual demonstration of how best to blow the spirometer. Subjects were relaxed, and dentures removed, tight fitting cloths loosened. Ambient temperature, barometric pressure and time of day and position of measurement were recorded. The time of day was within 2 hr of previous test times.
Although testing may be performed in either the sitting or standing position (Townsend 1984, ATS 1979), the sitting position was used for safety reasons in order to avoid falling due to syncope associated with pregnancy. The chair had arms and without wheels. The age, weight, height and ethnic origin of the subjects are keyed into the equipment and then customized to measure either the forced or the relaxed spirometric indices. Subject were instructed to sit upright in a straight backed chair, with belt loosened, breath normally for a minute , then take a deep breath as much as possible and apply the lip around the mouth piece of the spirometer firmly. She then breathes out as quickly and as forcibly as possible into the spirometer. Checks were made to ensure there were no leakages of air from the mouthpiece. Procedure was repeated if there was any leakage. The equipment automatically selects the best out of three maneuvers when the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines must have been met (three good blows with values within 5% or 0.15 litre (150 ml). The spirometer has an inbuilt mechanism that automatically rejects results associated with poor technique.
Prevention of infection transmission was achieved through proper hand washing and use of barrier devices, such as suitable gloves. Hands were washed immediately after direct handling of mouthpieces, tubing, breathing valves or interior spirometer surfaces. Gloves were worn when handling potentially contaminated equipment if the practitioner has any open cuts or sores on his/her hands. Hands were always washed between patients. To avoid cross-contamination, breathing tubes, valves and manifolds were disinfected or sterilized regularly. Any other equipment that comes into direct contact with mucosal surfaces were disinfected, sterilized or, if disposable, discarded after each use.
3.10 Statistical Analysis.
Values were recorded percentages and mean ± standard deviation where applicable. Analyses of data were done using Statistical Package for Social Sciences (SPSS) version 11, graph pad prism version 5.02 and graph pad prism state mate version 2.00. Normality tests were performed and comparison of mean was done by the one-way analysis of variance (ANOVA) if data obeyed Gaussian distribution However where data did not obey Gaussian distribution, the kruskal Wallis test was used. These were however followed by Tukey,s honestly significant post hoc multiple comparison. The respiratory function indices in pregnancy were compared with the values found in the matched controls.
Out of the three hundred subjected recruited, 172 (40 control, 30 first trimester, 48 second trimester and 54 third trimester) met the ERS/ATS quality control. Sociodemographic characteristics of the subjects are represented in table 1.
Forces Vital Capacity (FVC) and Percentage Predicted FVC
The mean values for FVC and the percentage predicted are shown in table 4. For the percentage predicted the changes are mainly due to differences between control versus 2nd trimester (P=0.006) and control versus 3rd trimester (P<0.0001).
Forced Expiratory Volume in One Second (FEV1) and Percentage Predicted.
The mean values for FEV1 and the percentage predicted are shown in table 5. For the percentage predicted the changes were mainly due to differences between control versus 2nd trimester (P=0.033) and control versus 3rd trimester (P<0.0001).
Peak Expiratory Flow Rate (PEFR liters /second) and Percentage Predicted
The mean values for PEFR and the percentage predicted are shown in table 6. The changes in the percentage predicted was mainly due to differences between control versus 3rd trimester (P=0.021).
4.7 Ratio of FEV1/FVC (%) and the Percentage Predicted
The mean values for FEV1/FVC and the percentage predicted are shown in table 7. For the percentage predicted the changes were mainly due to differences between control versus 2nd trimester (P=0.033) and control versus 3rd trimester (P<0.0001).
Figure 7: Mean FEV in one second/FVC during pregnancy
All the subjects were within the reproductive age group and there were no significant changes between the age groups .The fact that the highest parity occurred in the control group represents a selection bias as most of those who met the selection criteria for the control population had completed their families. Expectedly, the chest circumference increased as pregnancy progressed. Earlier studies had demonstrated this phenomenon (Thomas et al., 1938, Gibson 1966, Broughton-Pipkin 2007).
During pregnancy, insufficient or excessive weight gain can compromise the health of the mother and foetus and also affect lung function.
All the subjects had formal education. Indeed the majority had secondary education as the least qualification. Again, this represents a selection bias, as the illiterates that were initially recruited had difficulties understanding the instruction to be followed during spirometry. Indeed, lack of understanding of the procedure also led to the inability of the most of the recruited subjects to meet the ERS criteria on quality control.
The FVC and the percentage predicted and the FEV1 and the percentage predicted were within normal range in both the non-pregnant and pregnant subjects. However, the values decreased significantly, as pregnancy progressed. Although some earlier studies did not demonstrate any significant change in these parameters during pregnancy (Puranik et al.,1994, Chhbra et al.,1988), however, majority and more recent studies agreed with our findings (Mokkapatti et al.,1991, Lui 1992, Neeraj et al.,2010 )
This study also demonstrated that PEFR was normal in all the subjects but decreased more significantly during pregnancy. Conversely, the percentage predicted values showed a significant decline. The findings in the PEFR from most studies varied wildly depending on the equipment and the geographic location. While some studies agreed with our findings (Mokkapatti et al.,1991, Puranik et al,.1995 , Neeraj et al.,2010 ), others did not illicit any significant decline (Brancazio et al., 1997,Salisu et al,. 2007).
The FEV1/FVC ratio increased significantly, as pregnancy progressed. In a study in northern India, this parameter also increased but none significantly (Neeraj et al.,2010).
It was noted that the magnitude of decrease in FEV1 during pregnancy was not as much as the decrease in FVC. The consequence of this differential change is the rise in the FEV1/FVC ratio.
The decrease in FVC in our study may be due to a comparative decrease in the negativity of the intrapleural pressure occasioned by an upward displacement of the diaphragm by the enlarging uterus (Shaikh et al 1983). Decrease in FEV1, and PEFR may be due to a decline in alveolar PCO2 (caused by hyperventilation). In the respiratory tract, hormonal changes stimulate the mucosal vasculature leading to the reduction in airway resistance. This leads to increased ventilation and decreased partial pressure of CO2. This may probably be due to the progesterone-mediated loosening of ligaments and relaxation of the bronchial muscles (Lyons and Anthonio 1959). Furthermore, the decrease in PEFR could be due to lesser force of contraction of main expiratory muscles like the anterior abdominal wall muscles and internal intercostals muscles (Phatak et al 2003). In addition, it has been demonstrated that reduced haemoglobin level in pregnancy causes muscle weakness and this significantly affects ventilatory muscles.(Puranik et al.,1995, Neerag et al., 2009). Majority of pregnant women in Nigeria are anaemic and this may negatively affect the strength of contraction of the respiratory muscles (Ogunbode 1984, Nwagha et al.,2009).
The reduced value for FVC, lower FEV1 with higher FEV1/FVC is an indication that some degree of ventilatory restriction occur during pregnancy in our environment (Pellegrino et al., 2005). This phenomenon is physiological process that results from the reduction in lung volume occasioned by the growing uterus. Indeed, a further decrease in lung volume occurs during the early phase of each uterine contraction, resulting from redistribution of blood from the uterus to the central venous pool. It is therefore pertinent that, this should be taken into cognizance during the diagnosis and treatment of pregnant women with respiratory disorders.
This study forms a baseline for the determination of changes in some ventilatory function parameters during pregnancy in Enugu; South East Nigeria. The decreased FVC, PEFR, FEV1 and increased FEV1/FVC ratio is a strong indication that pregnancy causes physiological restriction in the lungs. With the combination of increased oxygen consumption and the decreased expiratory reserve volume due to the reduced functional residual capacity, rapid fall in arterial oxygen tension despite careful maternal positioning and pre oxygenation may occur during labour and spinal anaesthesia. Even with short periods of apnea, either from obstruction of the airway or inhalation of a hypoxic mixture of gases, the gravida has little defence against the development of hypoxia. Furthermore, the increased minute ventilation, combined with decreased functional residual capacity hastens inhalatory induction or changes in the depth of anaesthesia when breathing spontaneously. The baseline values that we established are therefore critical and invaluable while performing these procedures in normal pregnant women, but more especially in women with compromised cardiopulmonary functions.
Table 1: Some Demographic Characteristics of the Subjects
30.07 ± 4.41
31.50 ± 3.76
Chest C (cm)
27.29 ± 2.82
Hip C (cm)
Waist C (cm)
C = Circumference, M= Meter. Kg = Kilogram, Cm=Centimeter,
BMI= Body Mass Index, MAC= Mid Arm Circumference.
Ns=non-significant (P >0.05), * P < 0.05).
Table 4: Mean and Standard Deviation (SD) Forced Vital Capacity FVC (liters) and Percentage Predicted (%).
Percentage Predicted (%)
2.55 ± 0.51d
Post-hoc multiple comparison; a versus c (P=0.11), a versus d (P=0.006), b versus c (P=0.026), e versus g (P=0.006), and e versus h (P<0.0001).
Table 5: Mean and Standard Deviation (SD) of Forced Expiratory Volume in One Second (FEV1, liters /s) and Percentage Predicted
Percentage Predicted FEV1 (%)
Post hoc multiple comparison; a versus d (P = 0.013), e versus g (P=0.033), e versus h (P<0.0001).
Table 6: Mean and Standard Deviation (SD) Peak Expiratory Flow Rate (PEFR) Liters and Percentage Predicted
Percentage Predicted PEFR (%)
93.4 ± 32.16e
a vs. b vs. c vs. d (P=0.883)
e vs. f vs. g vs. h ( P=0.014)
87.60 ± 5.98f
83.19 ± 15.46g
79.39 ± 20.90h
Post hoc multiple comparison e versus h (P= 0.021)
Table 7: Mean and Standard Deviation (SD) of FEV1/FVC (%) and Percentage Predicted
107.37 ± 3.88e
102.97 ± 1.24f
109.56 ± 5.33g
105.77 ± 5.82h
A versus d (P=0.013), e versus g and h (p=0.033)