Racial and ethnic differences in preterm birth: A complex,multifactorial problem

Preterm birth remains the leading cause of morbidity and mortality among nonanomalous neonates, and is a major public health problem. Non-Hispanic black women have a 2-fold greater risk for preterm birth compared with non-Hispanic white race. The reasons for this disparity are poorly understood and cannot be explained solely by sociodemographic factors. Underlying factors including a complex interaction between maternal, paternal, and fetal genetics, epigenetics, the microbiome, and these sociodemographic risk factors likely underlies the differences between racial groups, but these relationships are currently poorly understood. This article reviews the epidemiology of disparities in preterm birth rates and adverse pregnancy outcomes and discuss possible explanations for the racial and ethnic differences, while examining potential solutions to this major public health problem.     

Sudden fetal death in women with well-controlled, intensively monitored gestational diabetes.

An intensive antepartum monitoring system for women with gestational diabetes mellitus was evaluated over a 5-year period. Early diagnosis and liberal treatment with insulin was concomitantly followed with non-stress testing: weekly from 28 to 34 weeks' gestation and semi-weekly thereafter. Despite maternal euglycemia and satisfactory antepartum assessment, three fetal deaths occurred within 72 hours of reassuring fetal monitoring. Additionally, 24 (7%) fetuses were delivered on the basis of a low biophysical profile score (less than 6) at term. The stillbirth rate for women with gestational diabetes was 7.7/1000, whereas the stillbirth rate for nondiabetic low-risk patients was 4.8/1000. Women with gestational diabetes continue to be in a high-risk category for antepartum fetal death, requiring intensive monitoring with consideration for timely delivery.     

Stillbirth and neonatal outcomes in South Australia, 1991-2000

OBJECTIVES: The purpose of this study was to determine the effect of maternal factors associated with impaired placental function on stillbirth and neonatal death rates in South Australia. STUDY DESIGN: From 1991 to 2000, the South Australian Pregnancy Outcome Unit's population database was searched to identify stillbirths and neonatal deaths in women with maternal medical conditions during pregnancy and in twin and singleton pregnancies. RESULTS: Women with hypertension and carbohydrate intolerance and who smoked during pregnancy had an increased risk of stillbirth. Women with twin pregnancies had a significantly higher stillbirth rate than for singletons at each week of gestational age. An increase in stillbirth rate at later gestations was seen with singletons, with a similar trend in twins but rising from 36 weeks' gestation. CONCLUSION: There is a clinical correlation between maternal factors associated with impaired placental function and increased risk of stillbirth, suggesting that intrauterine fetal death represents the mortality end point in a spectrum of intrauterine hypoxia.     

The Preterm Prediction Study: sequential cervical length and fetal fibronectin testing for the prediction of spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network

OBJECTIVES: This study was undertaken to further elucidate the pathogenesis of preterm birth by means of traditional risk factors and new markers for preterm birth derived from the Preterm Prediction Study. STUDY DESIGN: A total of 3076 women (2929 with singleton gestations and 147 with twin pregnancies) were categorized according to the presence of risk factors including black race, low body mass index, the presence of bacterial vaginosis, and previous preterm birth. At 24 and 28 weeks' gestation cervical length was measured and categorized as short (25 mm). Vaginal and cervical fetal fibronectin concentrations were measured at 24, 26, 28, and 30 weeks' gestation and results were categorized as positive (>/=50 ng/mL) or negative (<50 ng/mL). RESULTS: At 24 to 26 weeks' gestation women with each of the risk factors were more likely to have positive fibronectin test results or to have a short cervix. Among women with negative fetal fibronectin results at 24 to 26 weeks' gestation those with a short cervix were more likely to have positive fetal fibronectin results at 28 to 30 weeks' gestation, and among those with normal cervical length those women who had positive fetal fibronectin results were more likely to have a short cervix at later evaluation. Most women who had positive fetal fibronectin results at 24 to 26 weeks' gestation had negative results at 28 to 30 weeks' gestation, whereas most but not all women who had a short cervix at 24 to 26 weeks' gestation still had a short cervix at 28 to 30 weeks' gestation. In each period women with both a positive fetal fibronectin result and a short cervix were at substantially increased risk of spontaneous preterm birth; women with either marker alone had intermediate and approximately equal risks of spontaneous preterm birth, and women without either marker had a low risk of spontaneous preterm birth. CONCLUSION: Regardless of other risk factors, a short cervix predicts a subsequent positive fetal fibronectin result, and a positive fetal fibronectin result predicts subsequent cervical shortening. These data do not support a single sequence of events leading to spontaneous preterm birth.     

Multiple gestations: timing of indicated late preterm and early-term births in uncomplicated dichorionic, monochorionic, and monoamniotic twins

In this work we review the indications for late preterm and early-term birth in uncomplicated dichorionic, monochorionic, and monoamniotic twin gestations. Uncomplicated dichorionic twins have optimal outcomes when delivered at 38 weeks' gestation. Monochorionic twins, however, are at greater risk for unexpected stillbirth, and a management plan of late preterm delivery (34-37 weeks) after informed consent is reasonable. Monoamniotic twins are at even greater risk for sudden intrauterine fetal demise, and it is recommended that these expectant mothers be managed by inpatient hospitalization with fetal testing 1-3 times per day and delivery between 32 and 34 weeks' gestation. Recommendations are also provided for the circumstance of single intrauterine fetal demise in a twin gestation.     

Stillbirth after nonstress testing

The authors' experience with stillbirth within one week of a reactive nonstress test was reviewed to determine the reliability of this test in postdates patients and general high-risk patients. The corrected stillbirth rates were the same in both groups. Thirty-three percent of stillbirths in postdates patients occurred as early as 41.5 weeks' gestation. The cause of stillbirth in postdates patients was not clear even after careful autopsy. In the general high-risk group, 60% of stillbirths were due to an acute event with the remainder due to chronic fetal compromise that was not predicted by the nonstress test. Induction at 41.5 weeks' gestation or more comprehensive fetal surveillance than weekly nonstress testing are possible approaches to the management of postdates pregnancy, which need to be further studied.     

Racial and ethnic disparities in universal cervical length screening with transvaginal ultrasound

Objective: Determine if race or ethnicity is associated with missed or late transvaginal cervical length screening in a universal screening program.

Methods: Retrospective cohort study of nulliparous women with singleton gestations and a fetal anatomical ultrasound from 16–24 weeks’ gestation from January 2012 to November 2013. We classified women into mutually exclusive racial and ethnic groups: non-Hispanic black (black), Hispanic, Asian, non-Hispanic white (white), and other or unknown race. We used log-binomial regression to calculate the risk ratio (RR) and 95% confidence interval (CI) of missed or late (≥20 weeks’ gestation) screening versus optimally timed screening between the different racial and ethnic groups.

Results: Among the 2967 women in our study population, 971 (32.7%) had either missed or late cervical length screening. Compared to white women, black (RR: 1.3; 95% CI: 1.1–1.5) and Hispanic (RR:1.2; 95% CI: 1.01–1.5) women were more likely to have missed or late screening. Among women screened, black (versus white) women were more likely to be screened late (RR: 2.2; 95% CI: 1.6–3.1).

Conclusions: Black and Hispanic women may be more likely to have missed or late cervical length screenings.     

Contribution of late fetal deaths to US perinatal mortality rates, 1995-1998

We analyzed US fetal death and linked infant birth-death certificate data for 1995-1998 to evaluate perinatal deaths (late fetal deaths [> or = 28 weeks' gestation] and early neonatal deaths [< or = 7 days of life]) by race, Hispanic ethnicity, state of residence, and selected demographic characteristics. We also compared components of perinatal mortality, late fetal deaths, and early neonatal deaths, by birthweight, gestational age, and selected maternal medical conditions during pregnancy. From 1995 through 1998, there were 221,767 fetal deaths at > or = 20 weeks' gestation and infant deaths at less than 1 year. Of these, 113,421 (51%) were perinatal deaths; late fetal deaths accounted for 47% of perinatal deaths. The total perinatal mortality rate declined 5.3%, from 7.5 to 7.1 per 1,000 live births plus late fetal deaths. Blacks experienced higher perinatal mortality rates than whites (rate ratio = 2.1). Among perinatal deaths > or = 28 weeks' gestation, the ratio of fetal to neonatal deaths was 3.4 among blacks and 2.4 among whites. State-specific rates ranged from 5.2 to 13.1 per 1,000 live births plus late fetal deaths. Although late fetal deaths are not included in routine statistics of pregnancy outcomes, these deaths represent a large proportion of adverse pregnancy outcomes. Surveillance of perinatal mortality provides a more complete picture of the health of women, fetuses, and newborns. Improving the quality of surveillance data regarding fetal deaths is essential for more effective use of these data. This information can be used to prevent excess perinatal deaths and reduce disparities in pregnancy outcomes among high-risk subgroups identified by individual and population characteristics.     

Rescue by birth: defective placental maturation and late fetal mortality

OBJECTIVE: To estimate the incidence and lethality of placental maturation defect, and to determine the impact of the pattern of placental dysfunction on the risk of recurrent stillbirth or maternal disease in later life. METHODS: Questionnaire and archival analysis of fetal deaths from placental dysfunction at 32-42 weeks (1975-1995 in Zurich), classified as chronic (parenchyma loss) or acute (maturation defect of the terminal chorionic villi). Population survey of 17,415 consecutive unselected singleton placentas (1994-1998 in Berlin). RESULTS: Of the 71 stillbirths, 34 were due to parenchyma loss and 37 to maturation defect. Parenchyma loss predominated in the first pregnancy (73.5% compared with 43.2%; P <.05). The risks of recurrent stillbirth and subsequent childlessness did not differ between the two groups. Eleven percent of mothers whose placenta had maturation defect had diabetes in the index pregnancy; none of the other women in the group developed diabetes over the 5-20-year observation period. In the population survey, incidence of maturation defect was 5.7%, and was associated with fetal death in 2.3% of cases. Normal placentas were associated with fetal death in 0.033%. CONCLUSION: Placental maturation defect can be a cause of fetal hypoxia. Although the risk of stillbirth is 70-fold that of a normal placenta, few affected fetuses actually die. The risk of recurrent stillbirth is tenfold above baseline and occurs mostly after 35 weeks' gestation.     

Prospective risk of stillbirth.

Some fraction of any cohort of fetuses alive at a given gestational age will ultimately die before birth. The residual prospective risk of stillbirth as a function of gestational age was calculated from records of the New York City Department of Health covering 370,051 reported births between 1987-1989, including 2454 stillbirths. In the general population, the prospective risk of stillbirth at 26 weeks was one in 150 and, because the time distributions of live births and stillbirths were not proportionate, the risk changed with gestational age. By 40 weeks' gestation, it was one in 475, rising progressively thereafter to one in 375 at 43 weeks. The prospective risk of stillbirth was elevated in certain ethnic groups and increased significantly with advanced maternal age, multiple gestation, and lack of prenatal care. The prospective risk of stillbirth is an important consideration in decisions regarding timing of delivery.     

Maternal medical disease: risk of antepartum fetal death

Although certain maternal medical conditions increase the risk of antepartum fetal death, improvements in medical and obstetric care have decreased the likelihood of stillbirth. This article examines the current stillbirth rates reported in pregnancies complicated by common medical diseases. The reported stillbirth rates are expressed as the number of stillbirths occurring at > or = 20 weeks of gestation per 1,000 births in patients with the condition. Overall, about 10% of all fetal deaths are related to maternal medical illnesses such as hypertension, diabetes, obesity, systemic lupus erythematosus, chronic renal disease, thyroid disorders, and cholestasis of pregnancy. The early recognition of maternal medical diseases provides an opportunity for increased surveillance and interventions that may lead to more favorable pregnancy outcomes.     

Life-table analysis of the risk of perinatal death at term and post term in singleton pregnancies

OBJECTIVE: This study was undertaken to estimate the cumulative risk of perinatal death associated with delivery at each gestational week both at term and post term. STUDY DESIGN: The numbers of antepartum stillbirths, intrapartum stillbirths, neonatal deaths, and surviving neonates delivered at between 37 and 43 weeks' gestation in Scotland, 1985-1996, were obtained from national databases (n = 700,878) after exclusion of multiple pregnancies and deaths caused by congenital abnormality. The numbers of deaths at each gestational week were related to appropriate denominators: antepartum stillbirths were related to ongoing pregnancies, intrapartum stillbirths were related to all births (excluding antepartum stillbirths), and neonatal deaths were related to live births. The cumulative probability of perinatal death associated with delivery at each gestational week was estimated by means of life-table analysis. RESULTS: The gestational week of delivery associated with the lowest cumulative risk of perinatal death was 38 weeks' gestation, whereas the perinatal mortality rate was lowest at 41 weeks' gestation. The risk of death increased more sharply among primigravid women after 38 weeks' gestation because of a greater risk of antepartum stillbirth. The relationships between risk of death and gestational age were similar for the periods 1985-1990 and 1991-1996. CONCLUSION: Delivery at 38 weeks' gestation was associated with the lowest risk of perinatal death.     

Obstetric intervention,stillbirth, and preterm birth

Despite widespread recognition that preventing preterm birth is the most important perinatal challenge facing industrialized countries, preterm birth has increased steadily in recent years. This article examines the relation between trends in preterm birth, preterm labor induction/cesarean delivery, stillbirth, and infant mortality. The recent rise in preterm birth in the United States and Canada has been mainly due to increases in mild preterm birth (34-36 weeks). Live births at 34 to 36 weeks' gestation have increased largely as a consequence of increases in preterm induction and preterm cesarean delivery among women at high risk for adverse pregnancy outcomes. Increased obstetric intervention at 34 to 36 weeks' gestation appears to have led to larger-than-expected temporal declines in stillbirth rates at this gestation. Infant mortality rates have declined overall and also among live births at 34 to 36 weeks' gestation. Obstetric intervention at preterm gestation, when indicated, can prevent stillbirth and reduce infant morbidity and mortality despite the increasing rates of preterm delivery.     

A novel tocolytic agent: effects of letrozole on gestational length and parturition time

The purpose of this study was to determine whether letrozole, a potent aromatase inhibitor, could prolong gestation and/or delay parturition in rats. Seventy-five rats were divided into five groups of 15 rats each. Group I and group II rats were administered letrozole orally at doses of 0.002 and 0.02 mg/kg/day from days 15 through 21 of pregnancy, respectively. Rats in group IA were administered a concomitant estradiol cyclopentylpropionate (ECP) injection on day 15 and 0.002 mg/kg letrozole in that same manner as for group I. Rats in group IIA were administered concomitant ECP on day 15 and 0.02 mg/kg letrozole in the same manner as for group II. The control group received sterile saline only. Study and control groups were compared with respect to gestational length, parturition time, fetal mortality rate, stillbirth rate, and fetal body weight. Oral administration of letrozole both at daily doses of 0.002 mg/kg/day (group I) and 0.02 mg/kg/day (group II) consistently prolonged gestation and parturition time. The values of stillbirth rate, fetal mortality rate, and fetal body weight of group I were similar to those in the control group; conversely, fetal mortality rate and stillbirth rate of group II were higher than those values in the control group, and fetal body weight of group II was lower than in the control group. It was observed that concomitant injection of ECP effectively reversed the deleterious effects of letrozole on gestational length, parturition time, fetal mortality rate, stillbirth rate, and fetal body weight. The results of this study indicate that the aromatase inhibitor letrozole can prolong gestation and delays parturition in rats. Its deleterious effects on parturition can be reversed by ECP injection.     

Diabetes in pregnancy: a population-based study of incidence, referral for care, and perinatal mortality

During 1979 and 1980 in Washington State, 260 infants (live births plus fetal deaths greater than or equal to 20 weeks' gestation) were born to women with preexisting diabetes mellitus, the equivalent to a population-based incidence of 2.1 per 1000 total births. One quarter of these women had non-insulin-dependent diabetes prior to pregnancy. The perinatal mortality rate for all infants of diabetic mothers in this series was 108 per 1000, which was eight times the state perinatal mortality rate. Only 45% of births occurred in the five tertiary centers in the state, whereas 39% occurred in hospitals that had fewer than six deliveries per year complicated by overt diabetes. The mortality rate was slightly, but not significantly, lower among infants born in referral hospitals than among those born in primary-level hospitals. Congenital malformations accounted for 43% of the 28 perinatal deaths, and fetal losses between 20 and 27 weeks' gestation accounted for another 21%. During the 2-year study period there were only three cases in which antepartum care in nonspecialty centers may have contributed to a perinatal loss.     

Perinatal Mortality in a Tertiary Obstetric Institution

At the Royal Women's Hospital, Melbourne in the 3 years 1987-1989 analysis of the records of 13,347 public patients revealed an overall perinatal wastage of 20.8 per 1,000 births. This seemingly high figure resulted from the fact that 45% of losses occurred in nonbooked and emergency admissions. Many patients were referred with major complications of pregnancy, especially gross prematurity, lethal congenital malformations and intrauterine deaths. During the 3-year period 74% of perinatal losses occurred before 33 weeks' gestation and only 10% were after 37 weeks. By comparison at a Victorian State level, 47% of perinatal deaths occurred before 33 weeks and more than 35% after 37 weeks' gestation. The major causes of perinatal wastage in both groups were similar. At the Royal Women's Hospital in the 3-year period lethal congenital abnormalities accounted for 19.1% of fetal wastage, premature labour, premature rupture of the membranes and cervical incompetence 16.2%, multiple pregnancy 14.7%, antepartum haemorrhage 14.0% and hypertensive disorders 9.7%. During the 3-year period 7.7% of hospital stillbirths were intrapartum compared to 27% for the State of Victoria. The stillbirth rate in Victoria has declined over the past decade, but to a lesser extent than the neonatal death rate. Over the 3-year period 1987-1989 the ratio of stillbirths to neonatal deaths was 3 to 2, and in 1989 there were nearly twice as many stillbirths as neonatal deaths (424 versus 240). Furthermore, 55% of stillborn infants in Victoria had birth-weights of more than 1,500 g compared to the Royal Women's Hospital figure of 36%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of parity on fetal mortality in prolonged pregnancy

OBJECTIVE: In England an estimated 50,000 inductions of labour at or beyond 41 weeks' gestation are conducted each year. However, the published evidence on the effect of parity on stillbirth in prolonged pregnancy is limited, and has produced conflicting data. The aim of this study is to evaluate the influence of parity on fetal mortality in prolonged pregnancies. STUDY DESIGN: Retrospective analysis of 145,695 singleton births with known parity and no malformation noted at birth to residents in the former North-East Thames Region, UK. The parity and gestation specific stillbirth risks and relative risks per 1000 ongoing pregnancies were calculated in relation to parity between 37 and 45 weeks. RESULTS: Before 41 weeks the stillbirth risk rose gradually but did not differ by parity. By 41 weeks there was a substantial increase in the stillbirth risk in nulliparous women but not in parous women. The pattern of rise is such that the stillbirth risk is 2.9 times higher (95% CI 1.06-8.19) in nulliparous women at >42 weeks' gestation. CONCLUSION: Being parous appears to have a protective effect on fetal mortality in prolonged pregnancy. These findings question the need for routine induction of labour at 41 weeks in parous women.     

Socio-economic, demographic and obstetric risk factors for late fetal death of unknown etiology in Lithuania: a case--referent study

BACKGROUND: The purpose of this study was to evaluate the association between third trimester unexplained prelabor fetal deaths and various socio-economic, demographic and obstetric factors in Lithuania. METHODS: A case-referent study on 58 women with third trimester fetal death and 116 women with live fetus at term was carried out. Inclusion criteria for women in the first group (cases) were: prelabor fetal death of unknown etiology, singleton pregnancy >26 weeks of gestation and intact fetal membranes. For each case two referent women were recruited, admitted during the same period in active phase of labor at term (>37 weeks of gestation) with intact fetal membranes and fetus alive. Data were obtained by interview, anthropometry and by reviewing the medical records. Several potential socio-economic, demographic and obstetrical risk factors for unexplained fetal death were investigated. RESULTS: Univariate analyses determined several factors that were associated with fetal death of unknown etiology: low educational level, single marital status, low income, etc. After secondary logistic regression analysis only three independent variables remained significantly associated with otherwise unexplained stillbirth: small for gestational age fetus (OR 29.6; 95% CI 6.2-141.6), low income (OR 7.4; 95% CI 3.1-17.6), and maternal white blood cell count more than 16,000/mm3 (OR 5.4; 95% CI 1.4-21.6). Body mass index, smoking, occupation of women and other evaluated parameters were not confirmed to be significant risk factors. CONCLUSION: Small for gestational age fetus, low income and elevated maternal white blood cell count are factors significantly associated with late prelabor fetal death in Lithuania.     

Racial disparity in stillbirth among singleton, twin, and triplet gestations in the United States

OBJECTIVE: We investigated the relationship between maternal race and stillbirth among singletons, twins, and triplets. METHODS: We conducted a retrospective cohort study on 14,348,318 singletons, 387,419 twins, and 20,953 triplets delivered in the United States from 1995 through 1998. We compared the risk of stillbirth between pregnancies of black and those of white mothers using the generalized estimating equations framework to adjust for intracluster correlation in multiples. RESULTS: The proportion of black infants was 16%, 18%, and 8% among singletons, twins, and triplets, respectively. Crude stillbirth rate among singletons was 6.6 per 1,000 and 3.5 per 1,000 for black and white fetuses, respectively. Among twins, 796 stillbirths (11.6 per 1,000) were recorded for black mothers versus 3,209 stillbirths (10.1 per 1,000) among white mothers, whereas among triplets there were 233 stillbirths, of which 39 stillbirths were black fetuses (24.6 per 1,000) and 194 stillbirths were white fetuses (10.0 per 1,000). Black singletons, twins, and triplets weighed 278 g, 186 g, and 216 g less than white fetuses, respectively (P <.001). Risk of stillbirth was elevated in black fetuses compared with white fetuses among singletons (adjusted odds ratio [OR] 2.9, 95% confidence interval [CI] 2.8-3.0) and twins (OR 1.3. 95% CI 1.2-1.4) but comparable among triplets (OR 1.2, 95% CI 0.7-2.1). This decreasing trend was significant (P for trend <.001). CONCLUSION: The disparity of stillbirths between black and white fetuses still persists among singletons and twins. Among triplet gestations, however, the 2 racial groups have a comparable risk level. Our findings highlight the need for a rigorous research agenda to elucidate causes of stillbirth across racial/ethnic entities in the United States. LEVEL OF EVIDENCE: II-2     

Maternal Perception of Fetal Activity and Late Stillbirth Risk: Findings from the Auckland Stillbirth Study

Abstract: Background: Maternal perception of decreased fetal movements has been associated with adverse pregnancy outcomes, including stillbirth. Little is known about other aspects of perceived fetal activity. The objective of this study was to explore the relationship between maternal perception of fetal activity and late stillbirth (≥ 28 wk gestation) risk. Methods: Participants were women with a singleton, late stillbirth without congenital abnormality, born between July 2006 and June 2009 in Auckland, New Zealand. Two control women with ongoing pregnancies were randomly selected at the same gestation at which the stillbirth occurred. Detailed demographic and fetal movement data were collected by way of interview in the first few weeks after the stillbirth, or at the equivalent gestation for control women. Results: A total of 155/215 (72%) women who experienced a stillbirth and 310/429 (72%) control group women consented to participate in the study. Maternal perception of increased strength and frequency of fetal movements, fetal hiccups, and frequent vigorous fetal activity were all associated with a reduced risk of late stillbirth. In contrast, perception of decreased strength of fetal movement was associated with a more than twofold increased risk of late stillbirth (aOR: 2.37; 95% CI: 1.29–4.35). A single episode of vigorous fetal activity was associated with an almost sevenfold increase in late stillbirth risk (aOR: 6.81; 95% CI: 3.01–15.41) compared with no unusually vigorous activity. Conclusions: Our study suggests that maternal perception of increasing fetal activity throughout the last 3 months of pregnancy is a sign of fetal well‐being, whereas perception of reduced fetal movements is associated with increased risk of late stillbirth. (BIRTH 38:4 December 2011)