Abstract
Introduction:
The incidence of neonatal mortality has declined over the past few decades, but it remains a major concern. Identifying risk factors associated with adverse outcomes may help prevent and manage neonatal morbidity and mortality. The study aimed to explore the associated antenatal risk factors among pregnant women delivering in a tertiary care hospital in South India with adverse neonatal outcomes.
Material and Methods:
This was a hospital-based, matched case-control study among pregnant women belonging to Puducherry and admitted for delivery. Cases were pregnant women who gave birth to adverse neonatal outcomes, while controls were pregnant women who gave birth to alive and healthy babies. Data was collected from various sources, primarily from medical records, and triangulated.
Results:
Adverse neonatal outcomes were ten times more if pregnant women had placental complications and seven times more for intrauterine growth restriction noted during pregnancy. Pregnant women referred from peripheral care centers had 1.6 times more risk of adverse neonatal outcomes. Prior hospital admission during the present pregnancy had a protective effect in the final adjusted analysis.
Conclusion:
Risk factors should be routinely monitored in all health centers. Women with high-risk pregnancies should be identified earlier, and appropriate care should be provided.
Keywords: Adverse neonatal outcomes, antenatal risk factors, Apgar score, low birth weight, neonatal death, NICU admission, preterm birth, stillbirth
BACKGROUND
An adverse neonatal outcome is defined as the occurrence of neonatal death, low birth weight, preterm birth, admission to neonatal intensive care unit, stillbirth, and/or low APGAR score. Adverse neonatal outcomes are a major public health concern in developing countries such as India.[1] Despite the reduction in the proportion of adverse neonatal outcomes over the years, India still records the highest number of neonatal deaths, stillbirths, and preterm births globally.[2] Prematurity and low birth weight are important causes of neonatal deaths contributing to an increase in infant mortality rate and under-5 mortality rate.[2,3] In India, the low birth rate is 117 per 1000 live births, and the stillbirth rate is 12.5 per 1000 births. In comparison with the national average, Puducherry, a Union Territory of India, has a higher low birth rate (128 per 1000 live births) and a slightly lower stillbirth rate (11.5 per 1000 births).[2] With over forty-three thousand deliveries in Puducherry, it is important to understand the antenatal risk factors to plan strategies to prevent adverse neonatal outcomes.
Adverse neonatal outcomes are directly related to mortality and morbidity of the newborn.[4] They directly affect the infant’s development and overall health as an adult.[5] A majority (78%) of these adverse neonatal outcomes can be prevented by employing feasible and cost-effective interventions.[6,7] The occurrence of an adverse neonatal outcome also has a negative impact on the new parents. Families with children born with adverse neonatal outcomes suffer depression, anxiety, stress, social isolation, and economic loss.[8] Moreover, it has a detrimental effect on the country’s economy, owing to increased health expenditure. Medical costs for newborns with adverse neonatal outcomes are higher than those without adverse outcomes.[9,10]
Over the past years, antenatal risk factors of each adverse neonatal outcome have been studied individually. They include a broad spectrum of modifiable and non-modifiable risk factors such as maternal age, socioeconomic and health status, and past and present medical and obstetric history. Since most adverse neonatal outcomes co-occur, it is vital to study them as a composite indicator for programmatic reasons. This study aimed to explore the associated antenatal risk factors among pregnant women delivering in a tertiary care hospital in South India with adverse neonatal outcomes.
MATERIALS AND METHODS
Study design and setting
This study was a matched case-control study based on medical records between January 2017 and June 2017. The study was conducted at the Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), a tertiary hospital in Puducherry, South India. The study was approved by the JIPMER Institutional Ethics Committee – Human Studies. The data were collected from the Department of Obstetrics & Gynaecology and Neonatology. Pregnant women admitted to the Department of Obstetrics & Gynaecology for delivery belonging to Puducherry were included in the study.
Case & controls
A case is defined as a pregnant woman who gave birth to a baby with one or more adverse neonatal outcomes during the study period. Adverse neonatal outcomes include:
Neonatal death – the death of a live-born infant, regardless of gestational age at birth, within the first 28 completed days of life reported at the hospital
Low birth weight – a birth weight of less than 2500g
Preterm birth – less than 37 completed weeks of gestation.
Stillbirth – the birth of a fetus weighing more than 500g with no evidence of life after birth.
Admission to Neonatal Intensive Care Unit (NICU) – Any live birth needing intensive care and admitted to NICU.
Low APGAR – APGAR score of less than seven after five minutes of the birth.
The controls were selected from the medical records of pregnant women belonging to Puducherry who delivered at the same hospital and had no adverse birth outcomes. Controls were selected in the ratio of 1:1 by matching age (±2 years) and date of delivery (±5 days).
Data collection and data management
Data from seven different sources were triangulated for this study [Figure 1]. All the cases with complete medical records during the study period were included, and their matched controls were identified. Initially, the list of pregnant women and their neonatal outcomes were collected from the Department of Obstetrics and Gynaecology confinement register. Primary identifiers such as hospital identity number, age of the pregnant women, and date of delivery; and their neonatal outcomes such as gestational age, pregnancy outcome, birth weight, APGAR score, and NICU admission were collected from the register.
Figure 1.
Data sources
Data from the Hospital Information System and monthly reports from the Department of Neonatology were referred to obtain missing data to resolve any data mismatch. Later, all the cases were enlisted, and the medical records were obtained from the Medical Records Department. On the availability of the medical records of the case, a matched control was selected from the initial list obtained. Finally, antenatal history, obstetric history, medical history, and neonatal outcome were extracted from the medical records. A predefined proforma was designed in Open Data Kit (ODK) for data collection.
Statistical analysis
Descriptive statistics were used to describe the sample and outcome variables. Continuous variables are presented as means (±SD) and were compared using Student’s t-test. Categorical variables are presented as percentages and were compared using the Chi-square test. Bivariate logistic regression was conducted, and independent variables with a P value of less than 0.2 were entered into multivariate logistic regressions to control the effect of confounding factors and for further analysis. Variables with a P value less than 0.5 were considered to have a significant association with adverse neonatal outcomes in multivariate logistic regressions. And the outcome is reported as an adjusted odds ratio (OR) with a 95% confidence interval (CI). All analyses were completed using Statistical Package for the Social Sciences (SPSS) version 22.0 (SPSS Inc., Chicago, IL).
RESULTS
During the study period, 7465 women were admitted for delivery at the hospital, of which 828 were from the Union Territory of Puducherry, India. Of 828 women, 238 cases were identified, i.e., women with an adverse neonatal outcome. Only 170 cases had complete medical records and all the required information. Hence, 170 matched controls were selected from the remaining 590 women. The flow diagram of the selection of cases and controls is shown in Figure 2.
Figure 2.
Flow chart of the study
Characteristics of cases and controls
The study has 170 matched case-control pairs (1:1). The cases and controls were similar for most of the socio-demographic variables. In both categories, the majority of the pregnant women were unskilled or belonged to an agricultural background. The average age of the pregnant women was 26 years, and the family income was INR 7956 ± 11905 [Table 1]. The clinical profile of the cases and controls are described in Table 2.
Table 1.
Socio-demographics data of pregnant women
| Variables | Cases (n=170) | Controls (n=170) | Total (n=340) | P |
|---|---|---|---|---|
| Mother’s age (in years) | 26.9±4.7 | 26.9±4.4 | 26.9±4.5 | 0.37 |
| Occupation | ||||
| Unskilled/Agriculture | 120 (70.6) | 119 (70.0) | 239 (70.3) | 0.46 |
| Semiskilled | 38 (22.4) | 33 (19.4) | 71 (20.9) | |
| Skilled/Professional | 12 (7.1) | 18 (10.6) | 30 (8.8) | |
| Family income (in rupees) | 6592±9601 | 9320±13726 | 7956±11905 | 0.34 |
| Years in marriage (in years) | 3.7±3.5 | 3.3±2.9 | 3.52±3.2 | 0.53 |
| Consanguineous marriage | 14 (8.2) | 18 (10.6) | 32 (9.4) | 0.49 |
Table 2.
Clinical profile of the pregnant women
| Variables | Cases (n=170) | Controls (n=170) | P |
|---|---|---|---|
| Obstetric History | |||
| Maternal gravidity | |||
| Primigravida | 82 (48.2) | 77 (45.3) | 0.59 |
| Multigravida | 88 (51.8) | 93 (54.7) | |
| Parity | |||
| Nulliparous | 128 (88.9) | 133 (78.2) | 0.81 |
| Primiparous | 26 (15.3) | 23 (13.5) | |
| Multiparous | 16 (9.4) | 14 (8.2) | |
| Previous Stillbirths | 11 (6.5) | 5 (2.9) | 0.12 |
| Previous livebirths | 68 (40.0) | 76 (44.7) | 0.38 |
| Neonatal deaths | 4 (2.4) | 7 (4.1) | 0.34* |
| Previous dead child | 6 (3.5) | 10 (5.9) | 0.30 |
| Abortion | 33 (19.4) | 33 (19.4) | 0.99 |
| Spontaneous abortion | 28 (16.5) | 23 (13.5) | 0.45 |
| Medical Termination of Pregnancy | 7 (4.1) | 12 (7.1) | 0.24 |
| Ectopic pregnancy | 2 (1.2) | 1 (0.6) | 0.99* |
| Gynecological history | |||
| Infertility | 16 (9.4) | 11 (6.5) | 0.32 |
| Infertility treatment | 11 (6.5) | 9 (5.3) | 0.64 |
| Irregular cycles | 11 (6.5) | 8 (4.7) | 0.48 |
| Past gynecological surgery | 16 (9.4) | 11 (6.5) | 0.32 |
| Gynecological disease | 22 (12.9) | 26 (15.3) | 0.53 |
| Medical history | |||
| Hypertension | 14 (8.2) | 14 (8.2) | 0.99 |
| Diabetes mellitus | 3 (1.8) | 1 (0.0) | 0.62* |
| Heart diseases | 3 (1.8) | 3 (1.8) | 0.99* |
| Bronchial asthma | 1 (0.6) | 3 (1.8) | 0.62* |
| Gestational diabetes mellitus | |||
| Present pregnancy | 25 (14.7) | 29 (17.1) | 0.55 |
| Past pregnancy | 3 (1.8) | 8 (4.7) | 0.13* |
| Gestational hypertension | |||
| Present pregnancy | 10 (5.9) | 11 (6.5) | 0.82 |
| Past pregnancy | 2 (1.2) | 9 (5.3) | 0.03* |
| Hypothyroidism | 26 (15.3) | 30 (17.6) | 0.56 |
| Bronchial asthma | 1 (0.6) | 3 (1.8) | 0.62* |
| Anemia | 92 (54.1) | 108 (63.5) | 0.09 |
| Eclampsia | |||
| Present pregnancy | 3 (1.8) | 1 (0.6) | 0.62* |
| Past pregnancy | 1 (0.6) | 2 (1.2) | 0.99* |
| Preeclampsia | |||
| Present pregnancy | 5 (2.9) | 1 (0.6) | 0.21* |
| Past pregnancy | 1 (0.6) | 2 (1.2) | 0.99* |
| Family history of chronic disease | 31 (18.2) | 31 (18.2) | 0.99 |
*Fisher’s Exact Test was used when at least one of the cells was <5
Association between risk factors and adverse neonatal outcomes [Table 3]
Table 3.
Association between risk factors and adverse neonatal outcomes
| Risk Factorsa | Unadjusted model | Final model | ||
|---|---|---|---|---|
|
|
|
|||
| Odds Ratio (OR) | P | Adjusted Odds Ratio (AOR) | P | |
| Previous Stillbirth | 0.44 (0.15, 1.29) | 0.12 | 3.75 (0.87, 16.12) | 0.07 |
| Gestational diabetes mellitus in a past pregnancy | 2.75 (0.72, 10.55) | 0.13 | 0.42 (0.09, 1.80) | 0.24 |
| Gestational hypertension in a past pregnancy | 4.69 (0.99, 22.07) | 0.03 | 0.37 (0.06, 2.28) | 0.37 |
| Anemia | 1.48 (0.96, 2.28) | 0.08 | 0.71 (0.44, 1.15) | 0.17 |
| Present Vaginal delivery | 1.56 (0.96, 2.53) | 0.07 | 0.47 (0.16, 1.37) | 0.16 |
| Present cesarean section | 0.66 (0.39, 1.14) | 0.14 | 0.81 (0.25, 2.60) | 0.73 |
| Present placental complications | 0.09 (0.12, 0.74) | 0.10 | 10.09 (1.90, 93.50) | 0.04 |
| Present intrauterine growth restriction | 0.12 (0.28, 0.54) | 0.002 | 7.39 (1.55, 35.23) | 0.01 |
| Present cross-referencing of patients to other specialties | 1.81 (0.74, 4.45) | 0.18 | 0.50 (0.18, 1.38) | 0.18 |
| Present hospital admission during the pregnancy | 3.85 (1.05, 14.06) | 0.05 | 0.17 (0.03, 0.93) | 0.04 |
| Present referred from peripheral centers | 0.23 (0.66, 0.85) | 0.03 | 1.61 (1.15, 18.43) | 0.03 |
| Oedema | 1.98 (0.97, 4.04) | 0.05 | 0.44 (0.19, 1.00) | 0.05 |
| Past preterm | 0.51 (0.20, 1.33) | 0.16 | 2.08 (0.67, 6.45) | 0.20 |
| Past intrauterine growth restriction | 6.18 (0.73, 51.91) | 0.12 | 0.20 (0.67, 6.45) | 0.26 |
| Past Rh Incompatibility | 0.49 (0.44, 0.54) | 0.06 | 0.00 (0.00) | 0.99 |
aFactors included are those that differed significantly between cases and controls (P<0.2) and those having a biological plausibility as potential confounders (irrespective of the P).
Risk factors related to previous pregnancy
In the bivariate logistic regression, history of stillbirth, preterm birth, Intrauterine Growth Restriction (IUGR), Gestational Diabetes Mellitus (GDM), Gestational Hypertension (GHTN), and Rh Incompatibility were found to be associated (P-value <0.2) with adverse neonatal outcomes. However, in the final model, none of the risk factors mentioned above was associated with adverse neonatal outcomes.
Risk factors related to present pregnancy
In the bivariate logistic regression, anemia, edema, placental complications, IUGR, cross-referencing of patients to other specialties, and hospital admission during the present delivery were associated with (P-value <0.2) adverse neonatal outcomes. In the final model, placental complications, IUGR, cross-referencing of patients to other specialties, and hospital admission during the delivery were found to be independently associated with adverse neonatal outcomes without collinearity.
Cases had ten times more risk of adverse neonatal outcomes if they had placental complications (adjusted odds ratio [AOR], 10.09; 95% confidence interval [CI], 1.9–93.5); and seven times risk of adverse neonatal outcomes if they had intrauterine growth restriction during the present pregnancy (AOR, 7.39; 95% CI, 1.5–35.2). Pregnant women referred from peripheral care centers had 1.6 times more risk of adverse neonatal outcomes (AOR, 1.61; 95% CI, 1.15–18.43). Prior hospital admission during the present pregnancy had a protective effect in the final adjusted analysis (AOR, 0.17; 95% CI, 0.03–0.93).
DISCUSSION
This study attempted to explore the associated antenatal risk factors among pregnant women with adverse neonatal outcomes. Most of the research conducted in the past has included risk factors for individual adverse neonatal outcomes. However, this study analyzed the collective effect of adverse neonatal outcomes. Among the risk factors studied, only the risk factors of the present pregnancy were associated in the adjusted model; and none of the risk factors of the past pregnancy was associated with adverse neonatal outcomes. One of the probable reasons for this phenomenon is that the medical records have detailed information about the present pregnancy, whereas details of past pregnancies were scarcely recorded. Only risk factors such as placental complications, intrauterine growth restriction, prior hospital admission, and admission on referral during the present pregnancy were associated with adverse neonatal outcomes after adjusting for confounding factors.
Placental complications have a profound impact on stillbirth and preterm birth. Even lesser degrees of placental separation are known to be associated with preterm birth, and the risk of stillbirth dramatically increases with severe placental separation.[11] Similarly, intrauterine growth restriction occurs due to various maternal, placental, and fetal factors causing inadequate maternal supply, decreased ability of the fetus to utilize supply, and abnormal placental function, increasing the risk of adverse neonatal outcomes.
The study site is a tertiary referral center; an increase in the number of high-risk patients admitted for safe confinement is expected. A higher percentage (25% to 52%) of referrals might be due to health staff’s knowledge and under-confidence due to a lack of resources.[12] Almost 10% of the women are referred to a tertiary care center, and stillbirth or neonatal deaths double in respect of referred women.[13] Prior admission for treatment in the present pregnancy has a protective effect on adverse neonatal outcomes. This phenomenon may be because cross-reference was also more in controls. Pregnant women with complications were provided with multidisciplinary care, avoiding the occurrence of an adverse neonatal outcome.
Only a few risk factors from the present pregnancy were associated with the adjusted model, and none of the risk factors from past pregnancies showed an association with adverse neonatal outcomes. Given the study’s limitation, it is clear that there might be insufficient information on past deliveries. From an epidemiological point of view, factors contributing to conflicting results may be due to small study populations and a lack of information about potential confounders. More extensive prospective studies are suggested to examine the association between adverse neonatal outcomes and antenatal risk factors.
This is probably the first study in Puducherry, India, to complement the evidence concerning the multiple adverse neonatal outcomes that surpass the previously reported studies with single adverse neonatal outcomes. One of the limitations of this study was that the data was primarily based on hospital-based medical reports. Hence, there is a possibility of information bias. Only a clinically relevant history of past pregnancy could be noted. In addition, the women’s ability to recall and level of education level could have played a significant role.
Furthermore, neonatal deaths that were recorded in the medical records were considered. No attempt was made to verify the status of the neonates after their discharge from the hospital.
CONCLUSION
Risk factors like placental complications, intrauterine growth restriction, prior hospital admission, and admission on referral during the present pregnancy were associated with the occurrence of adverse neonatal outcomes. Risk factors should be routinely monitored in all health centers. Women with high-risk pregnancies should be identified earlier, and appropriate care should be provided.
Ethical approval
Institutional Ethics Committee (Human studies), JIPMER, Puducherry (JIP/IEC/2017/0476). No personal identifiers have been retained. All procedures performed in the study were in accordance with the ethical standards of the institutional ethics committee and with the 1964 Helsinki declaration and its later amendments.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgement
We acknowledge Dr. Rahul Aggarwal and Dr. Chanchal Kumar, DM Residents at the Department of Neonatology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) Puducherry, for helping in the triangulation of data. We also thank Ms. K. Narmadha (Dip GNM) for helping with data entry. We especially thank the unit heads at the Department of OBG, JIPMER Puducherry, for permitting us to access the medical records.
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