To Study the Perinatal Outcomes in Pregnancy with Previous Stillbirth

INTRODUCTION

Stillbirth is one of the deadliest complications of pregnancy serving as a nightmare for obstetricians and a devastating event for the couple and family. According to WHO, a total of 2 million stillbirths take place across the globe every year with a proportion of 40% taking place during labor.¹ India is the largest contributor of stillbirth to globe having an annual incidence of 0.34 million amounting to a stillbirth rate of 13.2.²

Extremes of maternal age, hypertensive disorders of pregnancy, prematurity, fetal growth restriction (FGR) are important risk factors and predictors for stillbirth.³ The causative etiology of stillbirth is a complex interplay of multiple parameters, such as gestation age, care of antenatal services received, associated comorbid conditions, obstetric parameters, and place of birth.⁴ This intertwined interaction makes it difficult to predict subsequent stillbirth, optimize state-of-the-art intervention, and decide the ultimate level of care.

The challenge faced by a caregiver is to counsel regarding the index event and to define a strategy for the management of subsequent pregnancy in order to prevent the recurrence of stillbirth. Many times, the patients are not aware of the cause of stillbirth leading to recurrence and adversities in pregnancy outcomes in unsupervised subsequent pregnancies. Due to lack of performance of verbal autopsy, non-uniformity in records and reporting system of stillbirth in our country, leading to many times unknown status of the causation behind stillbirth to the obstetrician dealing with a pregnancy with a previous stillbirth. However, there is a bountiful of data regarding affirmation of high chances of recurrence of stillbirth seen in subsequent pregnancies, but still there is paucity of data with regards to gestational age-specific recurrence per se. The knowledge regarding this aspect can help us create gestational age-specific interventions to reduce stillbirth recurrence incidence.

Therefore, to strike a balance between the most outcome-oriented result and minimum interventions is the need of the hour.

We undertake this study to assess the rate of recurrence of stillbirth at our center, to stratify gestational age-specific risk factors for the recurrence of stillbirth and study the adverse perinatal outcomes associated with it.

OBSTETRICAL MANAGEMENT

RESULTS

We retrospectively analyzed the data of 2,357 deliveries at our tertiary care institute from a period of December 2020 to December 2022. A total of 67 patients were identified as having previous stillbirth. Complete records for two patients were not available and three patients did not deliver at our institute. So, a total of 62 patients were recruited for analytic study (Fig. 1).

When examined for demographic parameters, majority of the patients were in the age-group of 26–33 years (43%). Maximum number of patients had a parity of more than or equal to 2 (66%). After complete interrogation, it was found that 63% of the patients were having poor antenatal status in the form of infrequent or irregular visits (OR 1.44 95% CI (0.6767–3.0830) (Table 1). A significant finding was that out of these, 17% of the patients had two or more than two stillbirths in a previous pregnancy.

A major number presented with adverse outcomes in later duration of pregnancy, or during labor (41%), but however, a high proportion (37%) was booked at our hospital in early pregnancy. The observed incidence of adverse outcomes was lower in booked patients.

Adverse pregnancy outcomes were noted in 39 patients comprising of a proportion of 62%. About 10 patients landed in abortion (first and second trimester). Preterm birth was observed in eight patients, out of these five had preterm premature rupture of the membranes (PPROM); FGR was noted in six patients. The recurrence of stillbirth was observed in eight patients (OR 5.6320 95% CI 2.510–12.3375). On analysis of associated medical and obstetrical factors, hypertensive disorders of pregnancy and FGR were associated in equal frequency (30.4%) patients.

Detailed obstetric outcome of the study revealed that 23 patients had uneventful pregnancy outcome. The only major observation in patients belonging to uneventful pregnancy group was the occurrence of anemia and hypothyroidism in 60.3% and 56% females, respectively (Fig. 2).

A proportion of 32% of them had moderate anemia and 11% had severe anemia. Majority of these patients had early first trimester booking (55%) and in 23% of this group, early interventions like Ecosprin and Enoxaparin were started as per their history profile.

After delivery, prolonged NICU admission was present in six patients and three early neonatal deaths were seen in this adverse perinatal outcome group (Fig. 3).

A recurrence of stillbirth was observed in eight patients. When a detailed analysis into the direct causative factors in cases with recurrent stillbirth was done, there was one case of ruptured uterus, two cases of obstructed labor with one case associated with acute fatty liver of pregnancy, one had severe growth restriction secondary to severe preeclampsia, and three very preterm births. Three patients had hypertensive disorders in pregnancy (HDP), with recurrence seen in two females (Fig. 4).

DISCUSSION

Our analysis found that having prior stillbirth predisposes to recurrence and adverse perinatal outcomes. The recurrence of stillbirth was observed in eight patients (OR 5.6320 95% CI 2.510–12.3375). Our study demonstrated high odds for recurrence in pregnancies preceded by previous stillbirth. A multicentric study was done by Kathleen Lamont⁵ and associates for comparing the prospective risk of stillbirth between women with and without a stillbirth in their previous pregnancy, it was concluded that the estimated risk of stillbirth in a subsequent pregnancy for women with stillbirth and live birth in a first pregnancy were 2.5% and 0.5%, respectively. Another large retrospective cohort study published by S Bhattacharya et al. concluded that the odds of recurrence of stillbirth in a second pregnancy were found to be 1.94 (99% CI 1.29–2.92). RSB rate in our study was found to be 12.9%. Nijkamp et al.⁶ concluded that women having previous stillbirth have a two-fold increased risk of recurrence. They observed a recurrent stillbirth rate of 8.1 per 1000 females. Such patients should be counseled during bereavement care itself and must be encouraged for peri-conceptional care and early pregnancy booking.

A deeper insight into the cases led the authors to conclude that almost all the cases were preventable and early fetomaternal surveillance could have benefitted and prevented the tragedies. All the cases belonged to poor socioeconomic strata and had poor antenatal care coverage. According to the global data on causative factors, half of the stillbirths were associated with intrapartum factors. Lawn JE et al.⁷concluded that most of these deaths could be avoided with an increased access to skilled health care in time. Nijkamp et al. in their study also reported a declining risk of recurrence of stillbirth after 32 weeks, contrasting to our findings. Gestational age at recurrence was almost corresponding and coherent with previous stillbirth gestational age in 62% of our study. Sparse data are available regarding gestational age-specific recurrence risk, which needs to be further interrogated. There is a need for further large studies for assessing gestational age stratification, as this knowledge will help in better interventional strategies (Table 2).

Adverse perinatal outcome was noted in 62% of these patients (OR 1.7101; 95% CI 1.0183–2.8720). Around 16% patients had first and second trimester abortions and 12.9% had preterm birth. Preterm birth is the leading contributing factor to stillbirths across the globe. Recurring causes for preterm births such as hypertension, abruption and growth restriction are important etiological factors. The study by Liang et al.⁸ also noted preterm birth to be the most commonly occurring adverse outcome (16.2%) in pregnancy with previous stillbirth. At our center, there were 5% NICU admissions and out of the total NICU admissions, two required surfactant therapy. One neonatal death was subsequent to a convulsive episode in patient of GDM who got referred from adjoining primary health care (PHC). Early referrals therefore hold important role in improving perinatal care.

The noted adverse perinatal outcomes were in higher frequency in those patients who reported to us in the third trimester and had poor antenatal visits. According to the Cochrane database systematic review⁹ published in 2020, it was clearly inferred that a reduced number of antenatal care visits results in an increase in perinatal death (RR 1.14 95% CI 1.00–1.31). The data were representative of five randomized control trials, which included 56,431 women. In the present study, 63% of the patients were found to be presenting in later duration of pregnancy, or during labor (41%). The complicating associated factors have already done the damage and little can be offered to prevent such mis-incidents. The WHO proposes five visits for optimizing pregnancy outcomes based on large antenatal trial initiated in the year 2000. A secondary analysis of this WHO Antenatal Care Trial¹⁰ found an increased relative risk of fetal death of 27% between 32 and 36 weeks gestation in populations with reduced antenatal care schedules. As per a study done by Kameswaran et al.¹¹ a five times higher risk of stillbirth occurs in emergency cases similar to Al-Kadri et al.¹² study who observed 70% risk of stillbirth in patients not receiving early antenatal care. In our study, we inferred a similar observation. Thus, in our country, a tailored number of antenatal care visits should be planned, especially in such a high-risk group. This is further supported by our observation that around 37% patients were booked at our hospital in early pregnancy and the rates of adverse incidents were lower in this group as compared with unbooked cases.

In this present study, most of the study subjects were in the age-group 26–35 years, thus indicating a high vulnerability to adverse outcomes associated with previous stillbirth in this age bracket. Extremes of age are a commonly reported risk factor for stillbirth.¹³ Our observation indicates that stillbirth has probably occurred at an earlier maternal age and thus recurrence happened in later age-group. This corroborates with the similar observation done by the author in the previous research, where teenage pregnancy was highly associated with intrauterine fetal demise (IUFD).

When associated complicating factors were analyzed, hypertensive disorders of pregnancy were found to have a major causal relationship.¹⁴ Jamal et al. in their study also noted HDP to be single most dominant complicating factor. In India hypertension is the major cause for maternal morbidity and mortality. Reports around establishment of hypertension with recurrent stillbirth are sparse and patchy. More prospective analytical studies will give a robust insight on this factor.

In our analysis, we found that some or the other cause was associated with recurrent stillbirth. Fetal growth retardation and prior unexplained stillbirth are two major predictors for recurrence in future pregnancies. Nonetheless, de novo appearance of other causative factors, level of antenatal care, place of birth, and planned interventions can decrease the rates. Thus, evaluation of the probable cause of fetal demise is of utmost importance. Modifiable etiologies are best dealt by strategizing optimum peri-conceptional care. Our study was limited by not performing of autopsy and tissue evaluation in these cases. Therefore, further testing into such cases to identify multifactorial etiology to carry out optimum and timely interventions is warranted.

CONCLUSION

Barring the fetal losses that took place inadvertently, most of the causes that were ascertained to be associated with adverse fetomaternal outcome in our study were preventable. This impetrates our need to understand the modifiable etiology of stillbirth and to strengthen the need of optimum antenatal care in order to timely identify the risk factors. In addition, the necessity of pre-conceptional counseling in order to avoid complications and recurrence must also be emphasized. Knowledge of the gestational age and causative etiology of previous stillbirth can serve as a good predictor, marker and guide for optimizing the outcome. Quality focused antenatal care, intrapartum care, and timely interventions can help reduce the incidence of recurrent stillbirth.

REFERENCES

1. Graham N, Stephens L, Johnstone ED, et al. Can information regarding the index stillbirth determine risk of adverse outcome in a subsequent pregnancy? Findings from a single-center cohort study. Acta Obstet Gynecol Scand 2021;100(7):1326–1335. DOI: 10.1111/aogs.14076.

2. United Nations Inter-agency Group for Child Mortality Estimation (UN IGME), ‘Levels and Trends in Child Mortality: Report 2020, Estimates developed by the United Nations Inter-agency Group for Child Mortality Estimation’, United Nations Children’s Fund, New York, 2020.

3. Maslovich MM, Burke LM. Intrauterine Fetal Demise. [Updated 2022 Oct 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023.

4. Lavin T, Pattinson RC. Does antenatal care timing influence stillbirth risk in the third trimester? A secondary analysis of perinatal death audit data in South Africa. BJOG 2018;125(2):140–147. DOI: 10.1111/1471-0528.14645.

5. Lamont K, Scott NW, Jones GT, et al. Risk of recurrent stillbirth: systematic review and meta-analysis. BMJ 2015;350:h3080. DOI: 10.1136/bmj.h3080.

6. Nijkamp JW, Ravelli ACJ, Groen H, et al. Stillbirth and neonatal mortality in a subsequent pregnancy following stillbirth: a population-based cohort study. BMC Pregnancy Childbirth 2022;22(1):11. DOI: 10.1186/s12884-021-04355-7.

7. Lawn JE, Blencowe H, Waiswa P, et al. Stillbirths: rates, risk factors, and acceleration towards 2030. Lancet 2016;387(10018):587–603. DOI: 10.1016/S0140-6736(15)00837-5.

8. Xiong T, Mu Y, Liang J, et al. Hypertensive disorders in pregnancy and stillbirth rates: a facility-based study in China. Bull World Health Organ 2018; 96(8):531–539. DOI: 10.2471/BLT.18.208447.

9. Ota E, da Silva Lopes K, Middleton P, et al. Antenatal interventions for preventing stillbirth, fetal loss and perinatal death: an overview of Cochrane systematic reviews. Cochrane Database Syst Rev 2020;12(12):CD009599. DOI: 10.1002/14651858.

10. World Health Organization (WHO). WHO Recommendations on Antenatal Care for a Positive Pregnancy Experience: Summary. Geneva, Switzerland: WHO; 2018. Licence: CC BY-NC-SA 3.0 IGO.

11. Kameswaran C, Bhatia BD, Bhat BV, et al. Perinatal mortality: a hospital based study. Indian Pediatr 1993;30(8):997–1001. PMID: 8125589.

12. Al-Kadri HM, Tamim HM. Factors contributing to intra-uterine fetal death. Arch Gynecol Obstet 2012;286(5):1109–1116. DOI: 10.1007/s00404-012-2426-z.

13. Patel S, Thaker R, Shah P, et al. Study of causes and complications of intra uterine fetal death (IUFD). Int J Reprod Contracept Obstet Gynecol 2014;3:931–935.

14. Shehla J, Shelly A. IUFD incidence, causes and complications: a retrospective study done at a tertiary care centre in greater Noida, India. Int J Reprod Contracept Obstet Gynecol 6. 5483. DOI: 10.18203/2320–1770.ijrcog20175265.