key: cord-0931487-7acpc0ct
authors: Naqvi, Seemab; Naqvi, Farnaz; Saleem, Sarah; Thorsten, Vanessa R.; Figueroa, Lester; Mazariegos, Manolo; Garces, Ana; Patel, Archana; Das, Prabir; Kavi, Avinash; Goudar, Shivaprasad S.; Esamai, Fabian; Mwenchanya, Musaku; Chomba, Elwyn; Lokangaka, Adrien; Tshefu, Antoinette; Yousuf, Sana; Bauserman, Melissa; Bose, Carl L.; Liechty, Edward A.; Krebs, Nancy F.; Derman, Richard J.; Carlo, Waldemar A.; Hibberd, Patricia L.; Billah, Sk Masum; Peres‐da‐Silva, Nalini; Haque, Rashidul; Petri Jr, William A.; Koso‐Thomas, Marion; Nolen, Tracy; McClure, Elizabeth M.; Goldenberg, Robert L.
title: Health Care in Pregnancy During the COVID‐19 Pandemic and Pregnancy Outcomes in Six Low‐and‐Middle‐Income Countries: Evidence from a Prospective, Observational Registry of the Global Network for Women’s and Children’s Health
date: 2022-04-04
journal: BJOG
DOI: 10.1111/1471-0528.17175
sha: 11a1da62de41395ebf7ff054834dd743973316ea
doc_id: 931487
cord_uid: 7acpc0ct

OBJECTIVE: On a population basis, we assessed medical care for pregnant women in specific geographic regions of six countries before and during the first year of the COVID‐19 pandemic in relationship to pregnancy outcomes. DESIGN: Prospective, population‐based study. SETTING: Communities in Kenya, Zambia, the Democratic Republic of the Congo, Pakistan, India, and Guatemala. POPULATION: Pregnant women enrolled in the Global Network for Women’s and Children’s Health’s Maternal and Newborn Health Registry METHODS: Pregnancy/delivery care services and pregnancy outcomes in the pre‐COVID‐19 time‐period (March 2019‐February 2020) were compared to the COVID‐19 time‐period (March 2020‐February 2021). MAIN OUTCOME MEASURES: Stillbirth, neonatal mortality, preterm birth, low birth weight, maternal mortality RESULTS: Across all sites, a small but statistically significant increase in home births occurred between the pre‐COVID and COVID periods. (18.9% vs 20.3%, aRR 1.12 95% CI 1.05, 1.19). Also, a small but significant decrease in the mean number of antenatal care visits (4.1 – 4.0, p= <0.0001) was seen during the COVID‐19 period. Of outcomes evaluated, overall, a small but significant decrease in low‐birthweight in the COVID‐19 period occurred (15.7% vs 14.6%, aRR 0.94 (0.89, 0.99), but we did not observe any significant differences in other outcomes. There was no change observed in maternal mortality or antenatal haemorrhage overall or at any of the sites. CONCLUSIONS: Small but significant increases in home births and decreases in the ANC services were observed during the initial COVID‐19 period; however, there was not an increase in the stillbirth, neonatal mortality, maternal mortality, low birth weight or preterm birth rates during the COVID‐19 period as compared to the prior year. Further research should help elucidate the relationship between access to and use of pregnancy‐related medical services and birth outcomes over an extended period.

The impact of COVID-19 on pregnancy outcomes has been studied using different approaches. To assess the direct impact of COVID-19, pregnant women with documented COVID-19 infection have been compared to outcomes among women without documented COVID-19. [1] [2] [3] [4] This approach, such as in the paper by Villar et al, suggest that symptomatic or severe COVID-19 infections during pregnancy are associated with increases in adverse maternal and neonatal outcomes. 1 Another approach evaluates the indirect impact of the COVID-19 pandemic on outcomes through disruption of medical services. [5] [6] [7] [8] [9] [10] [11] [12] These studies generally compare services and outcomes from before the COVID-19 pandemic to a time during the pandemic. Since the time-periods compared are often long, these studies may take substantial time to accumulate sufficient data to accurately assess services and outcomes. To reduce time necessary to estimate the impact of a pandemic on health services, modelling is another approach used. For example, a modelling exercise using the Lives Saved Tool estimated a potential excess of 56,700 maternal and 1,157,000 child deaths assuming up to 45% coverage reductions in 118 countries for 6 months during the COVID-19 pandemic outbreak. 10 How precisely the modelling results reflect reality is often unknown. For that reason, to understand the indirect impact of the COVID pandemic on important pregnancy outcomes, it is crucial to collect actual data on health service utilization and pregnancy outcomes.

The influence of pandemics on health service delivery and demand, especially in countries where resources are already constrained, may be substantial. [13] [14] [15] [16] [17] Challenges to service delivery include lack of key commodities, staff reassignment, and diversion of equipment and supplies to emergency care.

Specific mitigation measures such as lockdowns and curfews can also disrupt the provision of and access to services. [6] [7] [8] Fear of contracting infection and lack of trust in the health-care system may also adversely affect the demand for services. For example, during the Ebola virus outbreak in west Africa, many hospitals were closed due to transmission concerns, while available health care staff and resources were reallocated from routine health services to care for those with the virus. 18, 19 Disruptions in access to health-care services during pandemics often disproportionately impact the most vulnerable populations, including pregnant women, neonates, and children, especially in resource-constrained settings. 8 To minimize the impact of the ongoing COVID-19 pandemic on essential health services, and in particular, upon women's and newborns' healthcare, it is essential to understand the impact of the COVID-19 pandemic on healthcare service delivery and on pregnancy outcomes. 20 As an example, a study from Nepal reported that the COVID-19 outbreak reduced coverage of health facility births, with significantly increased stillbirth and neonatal mortality rates. 15 In contrast, a report from Bangladesh reported no impact of the pandemic on services. 21 A systematic review by Chmielewska et al., which did not evaluate services, reported that compared to the pre-COVID period, in the COVID period, there was a significant increase in stillbirths, (OR 1.28, 95% CI 1.07-1.54) but no increase in preterm births, low birthweight, or neonatal deaths. 16 Vaccaro et al compared pregnancy outcomes in pre-lockdown time periods with those during the lockdown and found an increase in stillbirths (OR 1.33, 95% CI 1.04 -1.60) but no change in low birth weight. 11 In a review of 11 studies comparing preterm births and low birthweight and associated outcomes in the pre-COVID-19 and during lockdown periods, we found no consistent relationship of the lockdowns to birth outcomes. 12 Few reports included in the above studies were population-based, and few originated in low-resource settings. Nevertheless, they raised questions about the indirect impact of the COVID-19 pandemic on maternal and neonatal health outcomes in resource-constrained settings. To facilitate understanding of the impact of the COVID-19 pandemic on perinatal health care, we used an ongoing population-based database to compare access to pregnancy and delivery care by pregnant women, and pregnancy outcomes in seven sites in six low and middleincome countries before and during the pandemic.

The Eunice Kennedy Shriver's Global Network for Women's and Children Health's (Global Network) Maternal and Newborn Health Registry (MNHR) is a prospective, population-based observational study which was initiated in 2009. 22, 23 All pregnant women in defined geographic communities which include approximately 300 to 500 births annually, are identified and enrolled. For this study, we analyzed population-based data from the 8 to 10 communities at the sites in western Kenya, Zambia (Kafue and Chongwe), the DRC (North and South Ubangi Provinces), Pakistan (Thatta in Sindh Provence), India (Belagavi and Nagpur) and Guatemala (Chimaltenango).

Registry administrators (RAs), trained study health care staff, identified pregnant women in their respective communities and following consent, enrolled them in the MNHR. 22, 23 Once a pregnant woman was identified, the RAs obtained basic health information at enrollment, recorded the date of last menstrual period (LMP) or early ultrasound report to assess gestational age, and other basic demographic information. A follow-up visit was carried out following delivery to collect information on pregnancy outcomes as well as the health care received during delivery. The maternal and newborn health statuses were collected at 42 days post-delivery.

The study outcomes were based on medical record reviews and birth attendant and family interviews.

Birth weights for babies born in facilities were available from the birth certificates or hospital records and for home deliveries, babies were weighed within 48 hours of birth by the RAs using standardized study scales. During the onset of the COVID-19 pandemic, some of the participating sites went through lockdown periods where the field activities were either partially or fully halted. However, the RAs continued to collect information on pregnancy and neonatal outcomes either through telephone contacts or by making home visits.

Stillbirths were defined as foetuses born at 20 weeks gestational age or more with no signs of life including movement, cry, or respirations. Neonatal deaths were defined as the death to any live-born infant, regardless of gestational age or birthweight, who died prior to 28 days of life. Maternal mortality was defined as death to the mother at any time in the pregnancy and up to 42 days post-partum. The outcome of miscarriages and medical terminations of pregnancy included any pregnancy registered in the MNHR that ended prior to 20 weeks gestation. Although we attempted to capture every pregnancy ending at 20 weeks or greater, some pregnancies, especially those with an early termination or miscarriage, may not be captured in the MNHR. Also, especially in Pakistan and Guatemala, the babies delivered in at home may not have been weighed because of the absence of personal contact due to the COVID-19 pandemic. However, most of the other data were collected by telephone in those sites.

The analysis population included women screened for the MNHR who were eligible, consented, and delivered at 20 weeks gestational age between March 2019 and February 2021. The pre-COVID-19 period was defined as extending from March 2019 through February 2020 and the COVID-19 period from March 2020 through February 2021, based on the World Health Organization's declaration of a global pandemic. 24 We compared the pregnancy and delivery care practices of women in the pre-COVID-Zambian and Kenyan sites as the African sites, and Belagavi and Nagpur, India, as the Indian sites.

Pakistan and Guatemala were considered separately.

The percent of women with >4 antenatal care (ANC) visits as well as the mean number of ANC visits in women at each site, the percent of deliveries by a physician and the percent of women delivering at home were analysed by site and year overall and for each of the two time-periods. Maternal mortality ratios, the rates of stillbirths, neonatal deaths until 28 days, early neonatal deaths <7 days, perinatal mortality defined as stillbirths plus early neonatal mortality, and low birthweight (LBW, <2500 g) and preterm birth (<37 weeks at delivery) were compared by site and overall, for both time-periods. The rates of stillbirth and perinatal mortality are reported per 1,000 live births and stillbirths, while neonatal mortality was calculated per 1,000 live births. For display purposes, the absolute changes in health care measures were calculated as the values during COVID-19 minus the pre-pandemic values.

Finally, we calculated the relative risks (RR) and corresponding 95% confidence interval (95% CI) from Poisson models for categorical variables and normal distribution model for continuous ANC visits with generalized estimating equations to account for the correlation of outcomes within community, accounting for site and the interaction of pre-or during COVID and site. We ran the same models adjusting for the potential confounders, maternal age, education, and parity. All statistical analyses were conducted in SAS v. 9.4 (SAS Institute, Cary, NC).

This study was reviewed and approved by ethics committees of participating research sites (INCAP, Guatemala; University of Zambia, Zambia; Moi University, Kenya; Aga Khan University, Pakistan;

Kinshasa School of Public Health, Kinshasa, DRC), KLE University's Jawaharlal Nehru Medical College, Belagavi, India; Lata Medical Research Foundation, Nagpur, India), the institutional review boards at each U.S. partner university and the data coordinating centre (RTI International). All women provided informed consent for participation in the study, including data collection and the follow-up visits.

Altogether, a total of 57,424 women were enrolled in the MNHR during the study periods. Of these, 57,396 consented to participate and birth outcome data were collected for 57,068 (99.4%) women ( Figure 1 ). Of these women, 29 . Finally, we found that the type of delivery attendant did not differ substantially between the two periods overall.

However, we observed increased physician-attended deliveries in the African sites and a decrease in the percent of physician-attended deliveries in Guatemala, changes that were statistically significant. There was also a slight increase in Caesarean births in the COVID period, which was significant overall (aRR 1.11, 95% CI 1.03, 1.19) and in Guatemala and India. In terms of measures of maternal health, we observed no statistically significant differences in the pre-COVID to during the COVID period. The maternal death ratio was 127/100,000 compared to 122/100,000 in the pre vs. COVID periods, respectively (RR 1.02, 95% CI 0.66, 1.59). Similarly, rates of antepartum and postpartum haemorrhage as well as reported hypertensive disorders were not significantly different in the two periods overall or by site.

We next evaluated the foetal and neonatal outcomes by period ( 

Our results, comparing data from the pre-COVID-19 period of March 2019 to February 2020 to the early COVID-19 pandemic period of March 2020 to February 2021, suggest that in most Global Network sites, there were small but significant increases in home births and small decreases in ANC utilization, and fewer deliveries (but not significantly fewer) attended by physicians. Importantly, there were no increases in the neonatal mortality, maternal mortality and stillbirth rates across the Global Network during the pandemic period compared to the prior year.

We have considered why, across the Global Network sites, we did not observe increases in stillbirths or neonatal deaths with the onset of the pandemic associated with the increase in home deliveries or the changes in antenatal care or physician attendance. First, the changes observed in ANC and care at delivery were all small. Second, we have previously explored the relationship between institutional delivery and stillbirth and neonatal mortality rates and did not find a consistent relationship across the Global Network sites. 25 We believe that the number of visits or site of delivery alone is not sufficient to establish a measure of obstetric or neonatal care quality. If high quality obstetric and neonatal care are not provided, delivering in a facility is unlikely to be associated with decreased fetal or newborn mortality.

We have also thought about why some other studies seemed to find large increases in certain poor outcomes associated with the COVID-19 pandemic, but this Global Network study did not. Most importantly, this was a population-based study of pregnancy outcomes over a time-period and did not evaluate the difference in outcomes between those women who tested positive for COVID-19 or were symptomatic and those women who tested negative. We were interested in whether changes in medical services for pregnant women occurred from prior to the pandemic to the early part of the pandemic and whether these changes were related to changes in outcome. We did not evaluate whether if a woman was infected with COVID-19 or if she was symptomatic, there were worse outcomes. We were especially interested in whether the very large increases in adverse outcomes associated with predictions of decreased services could be verified with actual data. Compared to some of the other studies evaluating care indices, our study included a large number of pregnancies from defined populations that were routinely monitored using standardized methods, and the results were less likely to be influenced by selection bias in outcomes or time-periods.

While maternal death and other adverse outcomes are increased with severe maternal COVID-19 infection, as evidenced by the study of Villar et al 1 , most maternal infections are mild and severe illness and death are rare. While occasional adverse outcomes occur, especially in populations with high rates of COVID-19 infections, for the most part, based on available evidence, we would not expect COVID-19

infections to have a substantial impact on stillbirths, neonatal deaths or maternal deaths at the population level. We recognize that the impact of COVID-19 on pregnancy and child outcomes is an ongoing area of active research. 20,26.27 Another potential explanation for the absence of change in stillbirth or neonatal mortality during the pandemic in our sites is that at least some pregnant women may have adopted behaviors that were protective against COVID-19, including less social interactions and more mask wearing that may have reduced their exposure to COVID-19. 28 The decreases in observed stillbirth rates in Guatemala and Pakistan may be actual, but also may have occurred due to decreased reporting of adverse outcomes due to reduced care seeking in those sites, especially early in pregnancy when most stillbirths occur. 29 The increases in stillbirths reported in the Vaccaro et al and the Chmielewska et al studies of about 30%, using methodologies different from this study, was not consistent with our findings and this difference requires further investigation. 11, 16 Strengths and limitations

Among the strengths of this study were the large sample size, population-based data from three regions, multiple sites, and prospective, on-going data collection with standardized data collection protocols across the sites. A limitation was the potential for decreased quality and completeness of data collection during the COVID-19 pandemic. However, extensive efforts were made to capture all pregnancy outcomes in Global Network geographic areas. We also had limited, objective assessment of the visibility of the COVID-19 pandemic at the onset for each community, and thus the time-periods when communities perceived the pandemic may have varied from the declaration by the WHO of the COVID-19 pandemic. Most important, the pandemic is still ongoing and likely increasing in severity and visibility in LMICs. Further evaluations will be required over time to determine whether observations made related to care seeking and pregnancy outcomes in the early stages of the pandemic hold through the remainder of the pandemic.

In summary, we emphasize the difference in some outcomes projected by some modeling exercises and the results of actual population-based data. Models, at times, can be useful in helping researchers consider the potential ranges in outcomes associated with potential changes in practice, especially if the estimates are reasonable. Estimates of very high rates of adverse outcomes based on extreme assumptions of decreased availability of medical care, may or may not, motivate the responsible governmental agencies or public health community into taking some action. However, when the population-based data fail to support the model's assumptions, credibility related to modeling may be lost.

In the Global Network sites, there was an increase in home births, and perhaps small decreases in ANC utilization and deliveries attended by a physician during the early COVID-19 period. Despite the differences in these measures of health care, we did not observe any mortality increases in the COVID-on a population basis will be important to better understand the indirect impact of the COVID-19 

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