Maternal morbidity in early pregnancy in rural northern Bangladesh

International Journal of Gynecology and Obstetrics 119 (2012) 227–233

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CLINICAL ARTICLE

Maternal morbidity in early pregnancy in rural northern Bangladesh Julia M. Kim a, Alain Labrique b, Keith P. West b,⁎, Mahbubur Rashid c, Abu A. Shamim c, Hasmot Ali c, Barkat Ullah c, Lee Wu b, Allan Massie b, Sucheta Mehra b, Rolf Klemm b, Parul Christian b a b c

Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, USA Center for Human Nutrition, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, USA JiVitA Maternal and Child Health and Nutrition Research Project, Gaibandha, Bangladesh

a r t i c l e

i n f o

Article history: Received 22 October 2011 Received in revised form 8 June 2012 Accepted 24 August 2012 Keywords: Bangladesh First trimester Maternal morbidity Low-resource country Pregnancy Prenatal

a b s t r a c t Objective: To determine the burden of maternal morbidity in early pregnancy in rural northern Bangladesh. Methods: A cross-sectional analysis was performed on baseline morbidity data from 42 896 pregnant women enrolled in a vitamin A supplementation trial. One-week histories for 31 defined symptoms were collected at 5–12 weeks of gestation. Ten illnesses were defined, compatible with ICD-10 diagnoses and WHO definitions. Prevalence, duration, and treatment-seeking behaviors were determined for each symptom and illness. Risk of wasting malnutrition was compared between symptomatic and asymptomatic women. Results: In total, 93.1% of women reported at least 1 symptom. The most frequent symptoms were poor appetite (53.3%), vaginal discharge (48.7%), and nausea (48.1%), each of which lasted 22–27 days. The most prevalent illnesses were anemia (36.4%), morning sickness (17.2%), excessive vomiting (7.0%), and reproductive tract infections (6.7%). Symptoms that prompted treatment seeking included jaundice, high-grade fever, and swelling of hands and face. Odds ratios for malnutrition were higher among women with symptoms of anemia (1.30; 95% confidence interval [CI], 1.24–1.36), vaginal discharge (1.37; 95% CI, 1.31–1.43), and high-grade fever (1.23; 95% CI, 1.10–1.37) than among those without symptoms. Conclusion: Women in rural Bangladesh report substantial morbidity in the first trimester. © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

1. Introduction Approximately 350 000 women die every year from pregnancyrelated causes [1,2]; 99% of these deaths occur in low-resource countries [3], where fewer than half of women receive adequate prenatal care [4]. The fifth Millennium Development Goal (MDG) proposes the reduction of maternal mortality by 75% and the prevention of morbidity through universal access to reproductive health services, including prenatal care, by 2015 [4]. However, little is known about the extent, severity, or consequences of morbidity during pregnancy in under-served societies [5,6]—especially during the first trimester, when pregnancy often proceeds undetected by the healthcare system [4]. Identifying the burden and patterns of early gestational maternal morbidity could both motivate efforts to provide earlier prenatal care and inform the public health agenda about preventive health interventions that could improve maternal and infant outcomes. Bangladesh illustrates the resources, burdens, and opportunities for improving reproductive public health. Routine maternal health services are provided by cadres of community workers who refer

⁎ Corresponding author at: Center for Human Nutrition, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, W-2041, Baltimore, MA 21205, USA. Tel.: +1 410 955 2061; fax: +1 410 955 0196. E-mail address: [email protected] (K.P. West).

mothers, as indicated, to satellite clinics, health clinics, and hospitals, where efforts are underway to improve home care practices, emergency obstetric services, and the overall quality of health care [7]. Mobile Health—which is the facilitation of effective healthcare education, outreach, and service provision through rapidly expanding mobile phone networks, as is occurring throughout many low-income countries—is a high priority for prenatal and obstetric services across rural Bangladesh [8,9], where nearly 90% of deliveries occur at home, 54% of women receive no formal prenatal care [10], and the first prenatal visit typically occurs at approximately 5 months of gestation. The situation restricts studies of maternal morbidity conducted through the health system to mid–late pregnancy and postnatal opportunities [11,12], leaving critical gaps in information on both maternal morbidity and informal prenatal healthcare use early in pregnancy in under-served rural settings. The aim of the present study was to report on the prevalence, duration, and severity of morbidity symptoms and illnesses during the first trimester of pregnancy in a typical rural population of northern Bangladeshi women. 2. Materials and methods The present study was a cross-sectional investigation of a cohort of pregnant women who were enrolled in a randomized, placebo-

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controlled community trial in northern Bangladesh from August 17, 2001, to October 12, 2006. The trial (clinicaltrials.gov No. NCT00198822) was conducted to assess the efficacy of weekly vitamin A or β-carotene supplementation in reducing maternal and infant mortality. The present study was approved by the Institutional Review Board of Johns Hopkins Bloomberg School of Public Health, Baltimore, USA, and the Bangladesh Medical Research Council, Dhaka, Bangladesh. Informed consent was obtained from all women included in the present analysis. Details of the design, procedures, and primary outcomes of the trial have been reported [13,14]. Women were identified prior to pregnancy and followed-up with home visits every 5 weeks to screen for pregnancy, before enrolling in prenatal care. Through this routine surveillance system, which spanned 596 local communities and regularly canvassed 125 257 women, pregnancies were identified at each visit through a history of amenorrhea and confirmed via a human chorionic gonadotropin urine test strip. The morbidity interview occurred within a few days of the identification of a pregnancy. Following administration of a standardized questionnaire (Supplementary Material S1), women were given weekly supplements of placebo, vitamin A, or β-carotene until 12 weeks post partum. Gestational age was estimated from a recalled date of last menstrual period, cross-checked against prospective menstrual histories. During the pregnancy enrollment interview, mothers were asked— using pretested local terms—about the occurrence and duration of 31 morbidity symptoms over the past 7 and 30 days, in addition to 5 further generalized symptoms for which only a 30-day history was obtained. Women were asked whether they sought treatment for each of the 31 morbidity symptoms, and if so from which type of provider. Women reporting symptoms for 3 or more days were referred to local, prescreened healthcare providers for clinical evaluation. Socioeconomic and pregnancy history data were also collected. The left mid-upper arm circumference (MUAC) was measured via standardized procedures using a non-stretch insertion tape [15]; a MUAC value of less than 21.5 cm represented wasting malnutrition [14]. A large number of trained female interviewers (n = 150, with 56 collecting 75% of all data) received data collection training and were supervised throughout the study in their execution of a standardized questionnaire [13]. They were routinely monitored and demonstrated reliability (Supplementary Material S2). Prior to completing each interview, staff checked data recorded on forms that were transmitted weekly to a data management center for entry according to reported procedures [13]. In the present analysis, morbidity was defined as either an individual symptom or an illness, and illness was defined by a combination of individual symptoms. Symptoms were considered to be present if they were reported during the previous 30 days and, conditioned on a positive response, the previous 7 days. To minimize underreporting, only 7-day reports were used to estimate morbidity burden. Symptoms were combined as clinical illnesses if they co-occurred during the previous week. Definitions of illnesses were adapted from WHO definitions [16] and the International Classification of Diseases, 10th Revision (ICD-10) [17]. Two adapted ICD-10 diagnoses relate specifically to early pregnancy (hemorrhage in early pregnancy and mild hyperemesis gravidarum), while others are general pregnancy-related diagnoses. To increase specificity, the definitions of reproductive tract infections (RTIs) and urinary tract infections (UTIs) incorporated the WHO syndromic approach to diagnosis, in addition to other potential presentations such as lower abdominal pain and high-grade fever. Abnormal bleeding was defined on the basis of reported vaginal spotting or "small amounts of bleeding" during each of the 7 previous days. The definition of hepatobiliary disease combined symptoms based on clinical judgment, which could reflect hepatitis, gall bladder infections, or gallstones. Anemia was defined, from WHO maternal screening questions [16], based on reported symptoms of breathlessness at rest and weakness resulting in an inability to work.

Symptomatic women were asked whether treatment was sought, as a proxy for evaluating severity of illness—especially in the study population, among whom care is not routinely sought [10,18]. Types of provider included shaman or religious healer; homeopath; ayurvedic; medicine shopkeeper; village doctor; paramedic; medical doctor; health clinic worker; or hospital staff. Providers were grouped together for the analysis to capture the intention of a woman to seek any treatment, presumably reflecting her concern about severity of illness and minimizing the influences of healthcare constraints imposed by distance or socioeconomic barriers. Women who did not seek treatment or used only home remedies were grouped together. For illnesses derived from combined symptoms, treatment seeking was defined as seeking care for at least 1 of the symptoms. The study design provided an opportunity to estimate the total number of days during which women experienced symptoms of illness during the first trimester. Prevalence was determined for each symptom. The mean duration of illness per gestational week was multiplied by the prevalence of the symptom for that gestational week, and products were summed, unweighted, across all firsttrimester weeks (weeks 5–12) to estimate total number of days with symptoms. This assumed that the prevalence and mean number of days of illness for a given week's sample of women represented the average morbidity burden in the rest of the cohort during the same week of gestation (i.e. each weekly stratum was representative of the cohort's experience). Statistical analysis was performed using Stata version 11 (StataCorp, College Station, TX, USA). The χ 2 test was used to compare characteristics of women included in the study versus those excluded and across each gestational week. Descriptive analyses revealed prevalence, symptom duration, and treatment-seeking frequencies. The t test was performed to test differences between MUAC measurement distributions in women with and without symptoms. Unadjusted and adjusted logistic regression analyses—accounting for maternal age, gestational age, parity, and socioeconomic status—estimated odds ratios for wasting malnutrition among women with and without morbidities. Analysis of variance tests compared continuous variables across multiple gestational age groups. Statistical significance was considered at P ≤ 0.05. 3. Results In total, 60 294 pregnant women were eligible for inclusion in the maternal supplementation trial cohort (Fig. 1). Consent was obtained, and pregnancy outcome and vital status were known for 59 666 (99.0%) women. Of these, 5791 (9.7%) did not complete the morbidity interview, mostly because of spontaneous abortion or stillbirth (n= 5528). Of the 53 875 women who completed the enrollment interview, 42 896 (79.6%) were interviewed within 12 weeks of gestation and within 7 days of supplementation in order to minimize potential nutrient effects on morbidity risk. In total, 10 979 (20.4%) women were excluded because their initial interview occurred after 12 weeks of gestation (n= 8543) or after the 7-day post-supplement window (n=2149), or because gestational age was unknown (n= 287). Among women included in the analysis, 14 652 (34.2%) were 19 years of age or younger (mean, 23.1 ± 6.3 years), all were between 5 and 12 weeks of gestation, 13 399 (31.2%) were nulliparous, and 10 964 (25.6%) had MUAC measurements of less than 21.5 cm (mean, 22.8 ± 2.0 cm) (Table 1). Overall, 22 480 (52.5%) women reported no formal education, while 17 456 (40.7%) reported being literate. The women interviewed and excluded from the analysis (n = 10 979) were more frequently 19 years of age or younger (n = 5688; 51.9%), nulliparous (n = 5916; 53.9%), and literate (n = 5676; 51.7%) compared with those included, in addition to being of higher socioeconomic means (0.09 vs −0.103) according to a local living standards index [19]. Characteristics of women, stratified by weekly gestational age, were comparable with regard to socioeconomic

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60 294 Pregnant women identified through surveillance in JiVitA-1 Vitamin A supplementation trial 573 Dosing consent not obtained 509 Refused interview consent 60 Not met/outcome occurred before consent obtained 4 Died before interview consent 55 Maternal vital status unknown at 12 weeks post partum 59 666 JiVitA-1 trial cohort, pregnant women consenting to study with known pregnancy outcome and maternal vital status 5791 Initial morbidity interview not completed, outcome prior to interview 5528 Spontaneous abortion/stillbirth 155 Live birth 93 Refused interview (29 consent, 64 interview) 15 Permanently moved, died before interview, lost to follow-up 53 875 Pregnant women completing initial morbidity interview 8543 Pregnancies > 12 weeks of gestation 287 Unknown gestational age 2149 Morbidity data collected > 7 days after supplementation given 42 896 First-trimester pregnancies with completed morbidity interviews Fig. 1. Flow chart of the selection of 42 896 pregnant women for analysis.

Table 1 Characteristics of women in the first trimester of pregnancy, Gaibandha, Bangladesh (n = 42 896).a Characteristic Maternal age at enrollment, y ≤19 20–29 ≥30 Gestational age, wk 1–4 5–8 9–12 ≥13 Gravidity 1 2 ≥3 Parity 0 1 2 ≥3 Mid-upper arm circumference, cm b18.5 18.5–21.4 21.5–26.4 ≥26.5 Maternal education, y None 1–9 ≥10 Religion Muslim Hindu Other Socioeconomic strata Literacy Income-earning job Living standards index [19] a b c

c

Women included in study (n = 42 896)

Women completing interview and excluded from study (n=10 979) b

P value

14 652 (34.2) 20 914 (48.8) 7308 (17.0)

5688 (51.9) 4220 (38.5) 1059 (9.7)

b0.001

0 (0.0) 19 212 (44.8) 23 684 (55.2) 0 (0.0)

2149 (20.1) 0 (0.0) 0 (0.0) 8543 (79.9)

b0.0001

12 319 (28.7) 9617 (22.4) 20 951 (48.9)

5631 (51.3) 2000 (18.2) 3344 (30.5)

b0.001

13 399 (31.2) 10 834 (25.3) 8016 (18.7) 10 638 (24.8)

5916 2152 1334 1574

b0.001

279 (0.6) 10 685 (25.0) 29 842 (69.7) 2011 (4.7)

59 (0.5) 2634 (24.0) 7830 (71.4) 441 (4.0)

22 480 (52.5) 17 602 (41.1) 2737 (6.4)

4488 (40.9) 5519 (50.3) 957 (8.7)

39 637 (92.4) 3180 (7.4) 70 (0.2)

10 042 (91.5) 903 (8.2) 32 (0.3)

17 456 (40.7) 6649 (15.5) −0.10 ± 0.96

5676 (51.7) 1508 (13.7) 0.09 ± 1.07

(53.9) (19.6) (12.2) (14.3)

b0.001

b0.001

b0.001

b0.001 b0.001 b0.0001

Values are given as number (percentage) or mean ± SD unless otherwise indicated. Percentages are calculated based on total number of women who responded to the question. Excluded owing to gestational age being greater than 12 weeks or unknown, or because morbidity data were collected more than 7 days after nutritional supplementation was given. χ2 test.

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status, nutritional status, and religious orientation; however, women with greater gestational age tended to be younger, have lower gravidity, and have higher levels of education (Supplementary Material S3). Arm circumference, which is an important covariate for health, remained stable. Women with MUAC measurements of at least 21.5 cm were slightly younger, of lower gravidity and parity, and of higher education and socioeconomic strata than women with MUAC measurements of less than 21.5 cm (Supplementary Material S4). The multivariate analysis adjusted for these differing characteristics. The most frequent symptoms were weakness resulting in an inability to work (n = 24 745; 57.7%), poor appetite (n = 22 858; 53.3%), vaginal discharge (n = 20 847; 48.7%), nausea (n = 20 597; 48.1%), breathlessness at rest (n = 18 735; 43.7%), low-grade fever (n = 16 394; 38.3%), lower abdominal pain (n = 10 371; 24.2%), and vomiting (n = 8472; 19.8%) (Table 2). Overall, 39 942 (93.1%) women reported at least 1 symptom. Two reported stool passing through the birth canal, for which neither sought treatment. Morbidity estimates by gestational age remained comparable for symptoms such as poor appetite (47.4%–58.1%), vaginal discharge (approximately 48%, except in week 12), nausea (40.3%–52.1%), low-grade fever (36.0%–42.3%), lower abdominal pain (23.3%–26.2%), and vomiting (14.4%–22.8%) (Supplementary Material S5). The highest

prevalence of reported nausea and poor appetite was observed at 9 weeks of gestation. The most prevalent symptoms also affected women for the greatest number of days. Women experienced, on average, poor appetite for 27.1 days, vaginal discharge for 25.5 days, nausea for 22.5 days, low-grade fever for 17.3 days, and lower abdominal pain for 8.9 days (Table 2). Symptoms for which the highest percentages of women sought treatment were jaundice (79.0%), swelling of hands (61.5%) or face (43.5%), yellow eyes (55.5%), high-grade fever (47.9%), diarrhea (38.9%), and blood or mucus in stool (31.2%) (Table 2). Other symptoms that prompted women to seek any treatment 10% to approximately 30% of the time included convulsions, lower abdominal pain, severe headache, rapid breathing, and vomiting—corresponding to WHO warning signs that warrant evaluation by a health provider [16]. Compared with asymptomatic women, those with low- or high-grade fevers, poor appetite, watery stools, vaginal discharge, tea-colored urine, jaundice, and night blindness had significantly lower MUAC measurements (P b 0.05) and higher relative odds of MUAC measurements less than 21.5 cm (Table 3). Women reporting face swelling, hand swelling (n = 13, with a 2.2-cm larger MUAC than those unaffected), nausea, lower abdominal pain, stress-related

Table 2 Prevalence, duration, and treatment-seeking behavior for reported maternal morbidity symptoms in the first trimester, Gaibandha, Bangladesh.a Morbidity symptoms

All women Prevalence

Generalized Weakness, inability to do work Breathlessness at rest Low-grade fever High-grade fever Facial swelling Hand swelling Gastrointestinal Poor appetite Nausea Lower abdominal pain Vomiting Bloody or mucoid stool Watery stool (≥4 times per day) Reproductive Vaginal discharge Painful and swollen breasts Vaginal spotting Uterine prolapse Urinary Painful urination Stress-related incontinence Continuously dripping urine Respiratory Cough Rapid breathing Blood in sputum Neurologic Severe headache Convulsions Hepatobiliary Tea-colored urine Liver/right upper quadrant pain Ash-colored/gray stools Jaundice Yellow eyes Nutritional deficiency Night blindness Any symptom/illness

b

Women with symptoms Total days ill

c

Days ill in past week

Treatment sought

Mean ± SD

Median (IQR)

24 745 (57.7) 18 735 (43.7) 16 394 (38.3) 1685 (3.9) 23 (0.05) 13 (0.03)

—d —d 17.3 1.1 0.03 0.02

—d —d 5.6 ± 2.0 3.4 ± 2.0 5.5 ± 2.0 5.5 ± 2.3

—d —d 7 (3) 3 (3) 7 (3) 7 (3)

—d —d 3027 (18.5) 796 (47.9) 10 (43.5) 8 (61.5)

22 858 (53.3) 20 597 (48.1) 10 371 (24.2) 8472 (19.8) 2489 (5.8) 806 (1.9)

27.1 22.5 8.9 5.9 1.9 0.4

6.6 ± 1.2 6.1 ± 1.8 4.6 ± 2.4 3.9 ± 2.5 4.1 ± 2.3 2.8 ± 1.9

7 (0) 7 (0) 5 (5) 3 (6) 3 (5) 2 (3)

3653 (16.0) 2059 (10.0) 1040 (10.0) 1136 (13.4) 769 (31.2) 311 (38.9)

20 847 (48.7) 1077 (2.5) 922 (2.2) 620 (1.4)

25.5 1.2 0.6 0.7

6.7 ± 1.1 6.0 ± 1.8 3.1 ± 2.1 6.3 ± 1.8

7 (0) 7 (2) 3 (3) 7 (0)

3548 (17.1) 136 (12.7) 113 (12.3) 167 (27.1)

4056 (9.5) 4087 (9.6) 481 (1.1)

3.8 2.6 0.5

5.0 ± 2.3 3.6 ± 2.4 5.2 ± 2.2

7 (4) 3 (6) 7 (4)

607 (15.0) 83 (2.0) 33 (6.9)

6398 (14.9) 1219 (2.8) 118 (0.3)

6.3 1.2 0.05

5.3 ± 2.1 5.4 ± 2.0 2.5 ± 2.1

7 (4) 7 (3) 1 (2)

1323 (20.8) 314 (25.9) 7 (5.9)

5553 (13.0) 190 (0.4)

4.3 0.2

4.3 ± 2.4 3.9 ± 2.6

4 (5) 3 (6)

1272 (23.1) 52 (27.4)

1374 (3.2) 750 (1.8) 453 (1.1) 239 (0.6) 200 (0.5)

1.3 0.6 0.3 0.2 0.2

5.7 ± 2.0 4.4 ± 2.5 3.8 ± 2.3 5.6 ± 1.9 5.8 ± 1.9

7 (3) 4 (5) 3 (5) 7 (3) 7 (3)

102 (7.4) 125 (16.7) 28 (6.2) 188 (79.0) 111 (55.5)

1238 (2.9) 39 942 (93.1)

1.6

6.6 ± 1.2

7 (0)

79 (6.4)

Abbreviation: IQR, interquartile range. a Values are given as number (percentage) unless otherwise indicated. Percentages are calculated based on total number of women who responded to the question. b The total number of women for whom morbidity history was available ranged from 42 715 to 42 891 for each symptom. c Based on composite analysis of 1-week morbidity data across gestational weeks 5–12. d Weakness resulting in inability to do housework and breathlessness at rest are additional generalized symptoms for which only 30-day prevalence data were collected.

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Table 3 Association of malnutrition with the presence of morbidity symptoms in the first trimester of pregnancy.a,b Individual symptoms

Difference in MUAC, cmc

OR for MUAC b21.5 cm Unadjusted OR (95% CI)

Generalized Low-grade fever High-grade fever Facial swelling Hand swelling Tires easily Breathlessness during routine work Gastrointestinal Poor appetite Nausea Vomiting Lower abdominal pain Bloody or mucoid stool Watery stool Reproductive Vaginal discharge Painful and swollen breasts Vaginal spotting Uterine prolapse Urinary Painful urination Stress-related incontinence Continuously dripping urine Respiratory Cough Rapid breathing Blood in sputum Neurologic Severe headache Convulsions Hepatobiliary Tea-colored urine Liver pain Ash-colored/gray stools Jaundice Yellow eyes Nutritional deficiency Night blindness Any symptom vs none

−0.15 ± 0.02e −0.19 ± 0.05e 0.99 ± 0.42f 2.22 ± 0.56e −0.32 ± 0.02e −0.28 ± 0.02e

1.13 1.23 0.61 —g 1.35 1.34

(1.08–1.18)e (1.10–1.37)e (0.21–1.80)

−0.08 ± 0.02e 0.07 ± 0.02e 0.01 ± 0.02 0.22 ± 0.02e −0.01 ± 0.04 −0.16 ± 0.07f

Adjusted OR (95% CI)d (1.09–1.20)e (1.10–1.37)e (0.20–1.80)

(1.29–1.42)e (1.28–1.40)e

1.14 1.23 0.61 —g 1.31 1.28

1.10 1.00 1.10 0.87 1.06 1.25

(1.06–1.15)e (0.96–1.04) (1.04–1.16)e (0.82–0.91)e (0.97–1.16) (1.07–1.45)f

1.13 1.05 1.16 0.93 1.04 1.21

(1.08–1.18)e (1.00–1.09) (1.09–1.22)e (0.88–0.98)f (0.95–1.15) (1.04–1.42)f

−0.41 ± 0.02e 0.08 ± 0.06 0.35 ± 0.07e 0.05 ± 0.08

1.44 0.96 0.87 1.02

(1.38–1.50)e (0.83–1.10) (0.75–1.02) (0.85–1.22)

1.37 1.05 0.91 0.97

(1.31–1.43)e (0.91–1.22) (0.78–1.06) (0.81–1.17)

0.02 ± 0.03 0.14 ± 0.03e −0.21 ± 0.09f

1.04 (0.96–1.12) 0.95 (0.89–1.03) 1.17 (0.96–1.43)

1.04 (0.97–1.12) 0.96 (0.89–1.04) 1.04 (0.85–1.28)

−0.002 ± 0.028 0.07 ± 0.06 −0.02 ± 0.19

1.06 (1.00–1.12) 1.02 (0.89–1.16) 1.10 (0.73–1.65)

1.08 (1.02–1.15)f 1.04 (0.91–1.19) 1.05 (0.69–1.59)

−0.03 ± 0.03 −0.39 ± 0.15f

1.08 (1.02–1.16)f 1.28 (0.94–1.74)

1.10 (1.03–1.17)f 1.16 (0.85–1.59)

−0.28 ± 0.06e 0.02 ± 0.08 0.040 ± 0.096 −0.43 ± 0.13e −0.33 ± 0.14f

1.24 1.08 1.07 1.37 1.23

−0.55 ± 0.06e −0.30 ± 0.04e

1.62 (1.44–1.82)e 1.48 (1.34–1.62)e

(1.10–1.39)e (0.91–1.26) (0.87–1.32) (1.04–1.80)f (0.90–1.66)

1.14 1.10 1.07 1.32 1.15

(1.25–1.37)e (1.23–1.34)e

(1.01–1.28)f (0.93–1.30) (0.86–1.32) (1.00–1.75) (0.85–1.57)

1.35 (1.20–1.53)e 1.47 (1.34–1.62)e

Abbreviations: CI, confidence interval; MUAC, mid-upper arm circumference; OR, odds ratio. a Values are given as mean difference ± SE unless otherwise indicated. b Malnutrition defined as MUAC less than 21.5 cm. c Mean difference in MUAC between women with symptoms and women without symptoms. d Adjusted for maternal age, gestational age, parity, and living standards index. e P ≤0.001. f P b 0.05. g Numbers were so small that computation was not possible.

incontinence, and vaginal spotting had significantly higher MUAC values (P b 0.05) (Table 3). Among composite illnesses, anemia (n = 15 621; 36.4%), morning sickness (n = 7396; 17.2%), excessive vomiting (n = 2983; 7.0%), and RTIs (n = 2894; 6.7%) were most prevalent (Table 4). Hepatobiliary problems (n = 46; 46.5%), pneumonia (n = 593; 44.5%), gestational edema (n = 11; 44.0%), gastroenteritis (n = 789; 38.3%), RTIs (n = 1033; 35.7%), and UTIs (n = 549; 28.3%) were most likely to prompt women to seek care. Anemia, RTIs, and excessive vomiting were associated with a lower MUAC measurement and significantly elevated risk of nutritional wasting (P b 0.001), after adjustment for age, gestational age, parity, and living standards index [19]. Women with gestational edema had significantly higher MUAC values (P = 0.01) than did women classified as non-edematous. 4. Discussion Previous studies have characterized maternal morbidities in late pregnancy [5,10,20–22], whereas the present study investigated morbidities occurring in the first trimester in a large cohort of women in

rural northern Bangladesh who rarely seek prenatal care in pregnancy [10,18]. The prevalence and duration of symptoms reveal a substantial burden of morbidity experienced by women on a population level. Mid-upper arm circumference measurements and treatment-seeking histories provide indications of severity of morbidity [22–25] and opportunities to validate reported morbidities indirectly. Women with symptoms of possible chronic duration or nutritional consequence (e.g. poor appetite, diarrhea, night blindness) tended to be nutritionally wasted, while those reporting edematous symptoms (e.g. face and hand swelling) tended to have a larger arm circumference. These symptoms may reflect a combination of antecedent risk of malnutrition coming into pregnancy, as well as a response to morbidity. Discerning the direction of these causal pathways is not possible in a cross-sectional analysis and will require longitudinal studies evaluating changes in MUAC and morbidity over time. The present estimates of morbidity are comparable to those obtained in an earlier study of first-trimester morbidity among 772 Nepalese pregnant women who had been participating in the placebo control arm of a vitamin A or β-carotene trial [5]. Comparable

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Table 4 Prevalence and associated risks of maternal illnesses based on combined reported symptoms (n = 42 896).a Illness

Anemia Morning sickness Reproductive tract infection Urinary tract infection Excessive vomiting (hyperemesis gravidarum) Gastroenteritis Pneumonia Abnormal bleeding Hepatobiliary disease

Gestational edema

Definition

Both symptoms present in the past 30 days: breathlessness at rest; and weakness Nausea and vomiting Vaginal discharge, lower abdominal pain, and high-grade fever; or vaginal discharge and painful urination Painful urination and lower abdominal pain; or painful urination and high-grade fever Vomiting on all of the past 7 days

Diarrhea (watery stools ≥4 times per day); bloody/mucoid stools and vomiting; or bloody/mucoid stools and lower abdominal pain Any 2 of the following: productive cough; rapid breathing; high fever Vaginal spotting on all of the past 7 days All 3 of the following: right upper quadrant (liver) pain; at least 1 symptom of elevated bilirubin or biliary obstruction (jaundice, yellow eyes, ash-colored stools, tea-colored urine); and at least 1 constitutional symptom (low-grade fever, poor appetite, nausea, vomiting) Swelling of hands or face

Prevalence

Treatment sought

15 621 (36.4) Info not collected 7396 (17.2) 1209 (16.4) 2894 (6.75) 1033 (35.72) 1939 (4.52) 549 (28.3)

Difference in MUAC, cmb

OR for MUAC b21.5 cm Unadjusted OR (95% CI)

Adjusted OR (95% CI)c

−0.28 ± 0.02d 1.36 (1.30–1.43)d 1.30 (1.24–1.36)d 0.02 ± 0.03 1.07 (1.01–1.13)e 1.14 (1.07–1.21)d −0.18 ± 0.04d 1.24 (1.14–1.35)d 1.22 (1.12–1.32)d 0.03 ± 0.05

1.05 (0.94–1.16)

1.06 (0.95–1.18)

2983 (7.0)

589 (19.8)

−0.07 ± 0.04

1.19 (1.09–1.29)d 1.22 (1.12–1.32)d

2063 (4.8)

789 (38.3)

−0.05 ± 0.04

1.13 (1.02–1.24)e 1.12 (1.01–1.24)e

1344 (3.1)

593 (44.5)

−0.02 ± 0.06

1.15 (1.02–1.30)e 1.17 (1.04–1.32)e

134 (0.3) 99 (0.2)

25 (18.9) 46 (46.5)

0.18 ± 0.18 −0.32 ± 0.20

0.85 (0.56–1.27) 1.41 (0.92–2.15)

0.84 (0.55–1.27) 1.31 (0.86–2.02)

25 (0.1)

11 (44.0)

1.03 ± 0.41e 0.56 (0.19–1.62)

0.54 (0.18–1.59)

Abbreviations: CI, confidence interval; MUAC, mid-upper arm circumference; OR, odds ratio. a Values are given as number (percentage) or mean difference ± SE unless otherwise indicated. Percentages are calculated based on total number of women who responded to the question. b Mean difference in MUAC between women with symptoms and women without symptoms. c Adjusted for age, gestational age, parity, and living standards index. d P b 0.001. e P b 0.05.

frequencies indicate stable and replicable burdens of these firsttrimester morbidities when collected by similar recall methods in rural settings along the northeastern Gangetic floodplain. The most prevalent symptoms involved the gastrointestinal system (nausea, vomiting, poor appetite, lower abdominal pain), reproductive system (vaginal discharge), and generalized symptoms (low-grade fever, weakness, breathlessness at rest). Symptoms such as nausea, vomiting, and breast pain or tenderness commonly occur during early pregnancy, reflecting normal physiologic hormonal changes. Other symptoms may reflect pre-existing or chronic conditions detected early in pregnancy, such as night blindness (due to chronic vitamin A deficiency) or hepatobiliary disease, although directionality of this association cannot be assessed from the present study. The prevalence results are probably underestimates, given that the data did not capture morbidity burden during the first 4 weeks because the earliest presentation was at 5 weeks of gestation. The analysis attempted to quantify the average number of prevalent days of morbidity in a population by assuming that women assessed in a given gestational week represented all women in the cohort during the same gestational week. As a crude index of magnitude, the estimates indicate a substantial burden of pregnancy, ranging from 9 to 27 days for the more common symptoms. For most morbidities, when treatment was sought, it was largely from non-allopathic or traditional providers. Despite the analytic attempt to minimize the effects of distance and cost in seeking treatment by grouping all providers together, the low rates of seeking treatment from either trained or traditional providers may reflect other social barriers faced by women early in pregnancy. The most prevalent composite illnesses included anemia (36.4%), morning sickness (17.2%), and RTIs (6.7%), which have been identified previously as important risk factors for adverse pregnancy outcomes. The high prevalence of reported anemia is comparable to other hemoglobin-based estimates, although gestational anemia in the present study population was related to hemoglobinopathies rather than iron deficiency [26]. The lower prevalence of morning

sickness may be accounted for by the definition requiring both nausea and vomiting in order to increase specificity, whereas many studies use nausea alone to report prevalence rates of 50%–90% [27]. The prevalence of RTIs probably does not reflect sexually transmitted infections, and instead captures women with normal physiologic discharge or endogenous infections such as bacterial vaginosis, which has been associated with preterm labor [28,29]. Urinary tract infections were reported in 4.5% of women and have been associated with pyelonephritis, preterm birth, and chorioamnionitis [29], thus underscoring the importance of identifying and treating UTIs during pregnancy. The findings of the present study were generated in a rural northern district (Gaibandha) that has previously been shown to reflect numerous features comparable to the national statistical profile of rural Bangladesh, including frequency distributions of women of reproductive age; their education and age at time of marriage; household asset characteristics; and types and availability of government health services [13]. Given the population-based surveillance system used to identify and enroll pregnancies, it may be reasonable to consider the estimates of morbidity to be broadly generalizable to other rural areas of the country for women who (based on their participation in the surveillance) would be likely to declare their pregnancy for early prenatal care. Also, because women who experienced spontaneous abortion or stillbirth were excluded, the findings are most applicable to the majority of women who deliver viable offspring. The strengths of the study derive from its population-based design, its large sample size, and the 7-day histories, which could be expected to minimize recall bias obtained via standardized methods by well-trained staff [13]. One limitation of the study was the use of self-reported morbidities that were not clinically and specifically validated. Also, the cross-sectional nature of the data does not enable the directionality of concurrent associations between malnutrition and morbidity to be determined. Finally, statistical significance may not reflect clinical significance, and with multiple comparisons chance associations may exist.

J.M. Kim et al. / International Journal of Gynecology and Obstetrics 119 (2012) 227–233

Nevertheless, in resource-limited settings, self-reported data— reported in a structured manner—often comprise the only available source of morbidity information and reflect community experiences seldom captured in clinic or hospital settings. Prenatal care addressing these reported health concerns may unveil underlying morbidities, and by treating illnesses in the first trimester women may be encouraged to use health services for illnesses throughout their pregnancy [6]. The present findings support the need to improve the delivery of scheduled prenatal care to detect and treat underrecognized morbidity early in pregnancy, and thereby accelerate progress toward MDG 5 [4]. Supplementary data to this article can be found online at http:// dx.doi.org/10.1016/j.ijgo.2012.06.022. Acknowledgments The present work was supported by a Micronutrients for Health Cooperative Agreement and Global Research Activity among the Johns Hopkins University and Office of Health, Infectious Diseases and Nutrition, US Agency for International Development (USAID), Washington DC (HRN-A-00-97-00015-00 and GHS-A-00-03-00019-00); "Global Control of Micronutrient Deficiency" Grant 614 from the Bill and Melinda Gates Foundation, Seattle, WA; the USAID Mission, Dhaka, Bangladesh; the Ministry of Health and Family Welfare, Government of Bangladesh; the Sight and Life Research Institute, Baltimore, MD; the Micronutrient Initiative/Canadian International Development Agency (CIDA), Ottawa, Canada; and the Nutrilite Health Institute, Access Business Group, Buena Park, CA. JMK was supported by the Agency for Healthcare Research and Quality (AHRQ) (T32 HS019488). Conflict of interest The authors have no conflicts of interest. References [1] Hogan MC, Foreman KJ, Naghavi M, Ahn SY, Wang M, Makela SM, et al. Maternal mortality for 181 countries, 1980–2008: a systematic analysis of progress towards Millennium Development Goal 5. Lancet 2010;375(9726):1609-23. [2] WHO, UNICEF, UNFPA, The World Bank. Trends in maternal mortality: 1990–2008 Estimates developed by WHO, UNICEF, UNFPA and The World Bank. http:// whqlibdoc.who.int/publications/2010/9789241500265_eng.pdf. Published 2010. [3] Ronsmans C, Graham WJ. Lancet Maternal Survival Series steering group. Maternal mortality: who, when, where, and why. Lancet 2006;368(9542):1189-200. [4] United Nations. Millennium Development Goals Report 2010. http://www.un. org/millenniumgoals/pdf/MDG%20Report%202010%20En%20r15%20low%20res%2020100615%20-.pdf. Published 2010. [5] Christian P, West KP, Khatry SK, Katz J, LeClerq SC, Kimbrough-Pradhan E, et al. Vitamin A or beta-carotene supplementation reduces symptoms of illness in pregnant and lactating Nepali women. J Nutr 2000;130(11):2675-82. [6] Filippi V, Ronsmans C, Campbell OM, Graham WJ, Mills A, Borghi J, et al. Maternal health in poor countries: the broader context and a call for action. Lancet 2006;368(9546):1535-41. [7] World Health Organization, John Snow. Country Profile on Reproductive Health in Bangladesh. http://www.searo.who.int/LinkFiles/Reporductive_Health_Profile_ chp-bangladesh.pdf. Published 2003.

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