Stillbirth recurrence in a population of relatively low-risk mothers

We sought to estimate the risk of stillbirth recurrence among relatively low-risk women, a group defined as maternal age <35 years; absence of congenital anomalies; gestational age range of 20–44 weeks inclusive; singleton births; and non-smokers. The Missouri maternally linked data containing births from 1978 to 1997 were used for the study. We identified the study group (low-risk gravidae who experienced a stillbirth in the first pregnancy) and a comparison group (low-risk gravidae who delivered a live birth in their first pregnancy) and compared the stillbirth risks in the second pregnancy between both groups. Analysis was based on 261 384 women with information on first and second pregnancies [1050 (0.5%) women with stillbirth].
Of the 947 cases of stillbirth in the second pregnancy, 20 cases occurred in women with a history of stillbirth (stillbirth rate 19.0 per 1000 births) and 927 in the comparison group (stillbirth rate 3.6 per 1000 births; P  < 0.001). The adjusted risk of stillbirth was almost six times higher in women with a prior stillbirth (hazard ratio [HR] 5.8, [95% CI 3.7, 9.0]). Analysis by stillbirth subtype in the second pregnancy showed that history of stillbirth conferred greater risk for subsequent early (fetal deaths between 20 and 28 weeks) (HR 10.3, [95% CI 6.1, 17.2]) than late stillbirths (fetal deaths at ≥29 weeks) (HR 2.5, [95% CI 1.0, 6.0]); and for intrapartum (HR 12.2, [95% CI 4.5, 33.3]) than antepartum (HR 4.2, [95% CI 2.3, 7.7]) stillbirths. Among relatively low-risk women, history of stillbirth was associated with increased recurrence, with substantial heterogeneity by timing of stillbirth.     

Electronic fetal monitoring in relation to cesarean section delivery, for live births and stillbirths in the U.S., 1980

In the 1980 National Natality and Fetal Mortality Surveys, information about fetal monitoring and type of delivery was obtained from hospitals for a sample of 9,941 live births and 6,386 fetal deaths of 28 weeks' gestation or more. Data in this analysis are weighted to provide national estimates of live births and late fetal deaths that occurred in U.S. hospitals during 1980. Electronic fetal monitoring (EFM) was used for 47.7 percent of live births; 27.2 percent were monitored by Doppler ultrasound only, 10.2 percent by scalp electrode only, 6.3 percent by Doppler ultrasound and scalp electrode only, and 4.0 percent by other methods and combinations. The distribution by type of EFM used was similar for the 42.7 percent of late fetal deaths (also called stillbirths) that were monitored. Variation in the use of EFM for live births and stillbirths is examined according to maternal age, parity, education, race, marital status, income, previous fetal loss, underlying medical conditions, complications of pregnancy, complications of labor, duration of labor, infant birth weight, and length of gestation. Among live births, 17.1 percent were delivered by cesarean section, as were 16.8 percent of stillbirths. The association between fetal monitoring and the primary cesarean section rate (the probability of cesarean section for women who had never had one) for all birth orders and for first births is examined according to characteristics of the mothers and the infants. Factors involved in the consistent association found between fetal monitoring and the primary cesarean section rate are discussed.     

A Case Series Study of Perinatal Deaths at One Referral Center in Rural Post-conflict Liberia

The overall objective of this study was to further our understanding of the factors contributing to the high perinatal mortality rates at a busy rural, referral hospital in Liberia. The specific aims were to: (1) analyze the records of women who experienced a perinatal loss for both medical and nonmedical contributing factors; (2) describe the timing and causes of all documented stillbirths and early neonatal deaths; and (3) understand the factors surrounding stillbirth and early neonatal death in this context. This case series study was conducted through a retrospective hospital-based record review of all perinatal deaths occurring at the largest rural referral hospital in north-central Liberia during the 2010 calendar year. A record review of 1,656 deliveries identified 196 perinatal deaths; 143 classified as stillbirth and 53 were classified as early neonatal death. The majority of stillbirths (56.6 %) presented as antenatal stillbirths with no fetal heart tones documented upon admission. Thirty-one percent of cases had no maternal or obstetrical diagnosis recorded in the chart when a stillbirth occurred. Of the 53 early neonatal deaths, 47.2 % occurred on day one of the infant’s life with birth asphyxia/poor Apgar scores being the diagnosis listed most frequently. Clear and concise documentation is key to understanding the high perinatal death rates in low resource countries. Standardized, detailed documentation is needed to inform changes to clinical practice and develop feasible solutions to reduce the number of perinatal deaths worldwide.     

Reliability of maternal recall and reporting of child births and deaths in rural Egypt

Demographic indicators such as fertility rates and infant mortality rates are often measured in census surveys by interviewing mothers to obtain their pregnancy histories and child deaths. The validity of such surveys depends upon accurate recall of histories, truthful reporting of events and understanding of the questions posed. To measure the reliability of maternal reporting, two census surveys conducted in a rural Egyptian population were compared. Women between 15 and 55 years of age residing in 20 villages were asked their histories of live births, stillbirths and child deaths. An identical set of questions was posed 2 years later. Twice-monthly home visits were conducted in the intervening 2-year interval to identify accurately any new births, stillbirths and deaths occurring in the population. The maternal reports from the first census were combined with the prospectively identified births, stillbirths and deaths and compared with the maternal reports from the second census. For 1502 women, the discrepancies in the total number of births, stillbirths and child deaths reported between the two surveys were 0.6%, 4% and 0.6% respectively. However, when the consistency of responses was analysed, the proportion of women with discordant responses was 10%, 6% and 7% for the same measures. These results suggest that, despite the large number of births and deaths that women may experience in developing countries, maternal interviews provide reliable responses that can be used to estimate mortality and fertility rates in settings where vital records are incomplete or unreliable.     

Fetal Deaths in Brazil: Historical Series Descriptive Analysis 1996–2012

Objective We seek to comprehensively assess stillbirths in Brazil, to compare the Brazilian findings with global trends and to identify the limitations of the fetal death record system. Method We studied fetal deaths in Brazil between 1996 and 2012 within the following five regions of the country: the North, Northeast, Southeast, South, and Central-West, through an analysis of data obtained from the Unified Health System’s (SUS) Informatics Department. The rates of stillbirth in Brazil and in these regions were calculated in relation to the maternal and gestational age and education, birth weight, type of pregnancy, delivery type, weight ranges and cause of death. Results There were 579,661 recorded fetal deaths and a decrease of 22.9 % in the stillbirth rate. In 2012, the overall rate was 10.0/1000 births; the North and Northeast regions had the highest rates (10.3 and 12.1, respectively) and the South region had the lowest rate (7.7/1000 births). Two-thirds of the deaths occurred in pregnancies of 28 or more weeks. Low education was an important risk factor, with rates of 24.3/1000 birth in women with no formal education and 4.7/1000 birth in women with 12 or more years of study in 2012. More than 40 % of the causes of deaths were nonspecific. Conclusions Despite the gradual decline in stillbirth rates, Brazil still has stillbirth rates that are nearly two times higher than those found in developed countries. There are inequalities between country regions portrayed by the significant variation in mortality rates specified by cause.     

Can clinical risk factors for late stillbirth in West Africa be detected during antenatal care or only during labour?

BACKGROUND: Recent studies have shown that the most important risk factors for perinatal mortality in developing countries are not detectable during antenatal care but can be observed only shortly before or during labour. Although 60% of perinatal deaths in these countries are stillbirths, few epidemiological studies focus on them. We tested the hypothesis that the risk factors for late stillbirth in West Africa are detectable principally shortly before or during labour. METHODS: Data came from a prospective population-based study (the MOMA survey) that collected information about 20 326 pregnant women in seven areas, primarily urban, in West Africa. RESULTS: There were 19 870 singleton births. The stillbirth rate was 25.9 per 1000 total births (95% CI: 23.7-28.1). In the crude analysis, after adjustment and consideration of prevalence, the principal risk factors for late stillbirth were: late antenatal or intrapartum vaginal bleeding, intrapartum hypertension, dystocia, and infection. Other risk factors were: maternal height (<150 cm), maternal age (>35 years), previous stillbirths, hypertension at the 8-month antenatal visit and number of antenatal visits (<2). CONCLUSIONS: The principal risk factors for late stillbirth observed in our study could be detected only in the late antenatal and intrapartum period. These results highlight the potential benefits of partograph use. They need to be confirmed by studies incorporating continuous intrapartum fetal monitoring.     

Cause-Specific Stillbirth and Neonatal Death According to Prepregnancy Obesity and Early Gestational Weight Gain: A Study in the Danish National Birth Cohort

Maternal obesity is associated with impaired fetal and neonatal survival, but underlying mechanisms are poorly understood. We examined how prepregnancy BMI and early gestational weight gain (GWG) were associated with cause-specific stillbirth and neonatal death. In 85,822 pregnancies in the Danish National Birth Cohort (1996–2002), we identified causes of death from medical records for 272 late stillbirths and 228 neonatal deaths. Prepregnancy BMI and early GWG derived from an early pregnancy interview and Cox regression were used to estimate associations with stillbirth or neonatal death as a combined outcome and nine specific cause-of-death categories. Compared to women with normal weight, risk of stillbirth or neonatal death was increased by 66% with overweight and 78% with obesity. Especially deaths due to placental dysfunction, umbilical cord complications, intrapartum events, and infections were increased in women with obesity. More stillbirths and neonatal deaths were observed in women with BMI < 25 and low GWG. Additionally, unexplained intrauterine death was increased with low GWG, while more early stillbirths were seen with both low and high GWG. In conclusion, causes of death that relate to vascular and metabolic disturbances were increased in women with obesity. Low early GWG in women of normal weight deserves more clinical attention.     

Prevalence of Hospitalized Live Births Affected by Alcohol and Drugs and Parturient Women Diagnosed with Substance Abuse at Liveborn Delivery: United States, 1999–2008

To describe prevalence trends in hospitalized live births affected by placental transmission of alcohol and drugs, as well as prevalence trends among parturient women hospitalized for liveborn delivery and diagnosed with substance abuse problems in the United States from 1999 to 2008. Comparison of the two sets of trends helps determine whether the observed changes in neonatal problems over time were caused by shifts in maternal substance abuse problems. This study independently identified hospitalized live births and maternal live born deliveries from discharge records in the Nationwide Inpatient Sample, one of the largest hospital administrative databases. Substance-related diagnosis codes on the records were used to identify live births affected by alcohol and drugs and parturient women with substance abuse problems. The analysis calculated prevalence differences and percentage changes over the 10 years, with Loess curves fitted to 10-year prevalence estimates to depict trend patterns. Linear and quadratic trends in prevalence were simultaneously tested using logistic regression analyses. The study also examined data on costs, primary expected payer, and length of hospital stays. From 1999 to 2008, prevalence increased for narcotic- and hallucinogen-affected live births and neonatal drug withdrawal syndrome but decreased for alcohol- and cocaine-affected live births. Maternal substance abuse at delivery showed similar trends, but prevalence of alcohol abuse remained relatively stable. Substance-affected live births required longer hospital stays and higher medical expenses, mostly billable to Medicaid. The findings highlight the urgent need for behavioral intervention and early treatment for substance-abusing pregnant women to reduce the number of substance-affected live births.     

Underreporting of maternal deaths on death certificates and the magnitude of the problem of maternal mortality

OBJECTIVES: I studied the extent to which maternal deaths are underreported on death certificates. METHODS: We collected data on maternal deaths from death certificates, linkage of death certificates with birth and fetal death records, and review of medical examiner records. RESULTS: Thirty-eight percent of maternal deaths were unreported on death certificates. Half or more deaths were unreported for women who were undelivered at the time of death, experienced a fetal death or therapeutic abortion, died more than a week after delivery, or died as a result of a cardiovascular disorder. CONCLUSIONS: The number of maternal deaths is substantially underestimated when death certificates alone are used to identify deaths, and it is unlikely that the Healthy People 2010 objective of reducing the maternal mortality rate to no more than 3.3 deaths per 100000 live births by 2010 can be achieved. Increasing numbers of births to older women and multiple-gestation pregnancies are likely to complicate efforts to reduce maternal mortality.     

Adverse birth outcomes in United Republic of Tanzania--impact and prevention of maternal risk factors

OBJECTIVE: To determine risk factors for poor birth outcome and their population attributable fractions. METHODS: 1688 women who attended for antenatal care were recruited into a prospective study of the effectiveness of syphilis screening and treatment. All women were screened and treated for syphilis and other reproductive tract infections (RTIs) during pregnancy and followed to delivery to measure the incidence of stillbirth, intrauterine growth retardation (IUGR), low birth weight (LBW) and preterm live birth. FINDINGS: At delivery, 2.7% of 1536 women experienced a stillbirth, 12% of live births were preterm and 8% were LBW. Stillbirth was independently associated with a past history of stillbirth, short maternal stature and anaemia. LBW was associated with short maternal stature, ethnicity, occupation, gravidity and maternal malaria whereas preterm birth was associated with occupation, age of sexual debut, untreated bacterial vaginosis and maternal malaria. IUGR was associated with gravidity, maternal malaria, short stature, and delivering a female infant. In the women who had been screened and treated for syphilis, in between 20 and 34% of women with each outcome was estimated to be attributable to malaria, and 63% of stillbirths were estimated as being attributable to maternal anaemia. Screening and treatment of RTIs was effective and no association was seen between treated RTIs and adverse pregnancy outcomes. CONCLUSION: Maternal malaria and anaemia continue to be significant causes of adverse pregnancy outcome in sub-Saharan Africa. Providing reproductive health services that include treatment of RTIs and prevention of malaria and maternal anaemia to reduce adverse birth outcomes remains a priority.     

Racial Disparities in Economic and Clinical Outcomes of Pregnancy Among Medicaid Recipients

To explore racial-ethnic disparities in adverse pregnancy outcomes among Medicaid recipients, and to estimate excess Medicaid costs associated with the disparities. Cross-sectional study of adverse pregnancy outcomes and Medicaid payments using data from Medicaid Analytic eXtract files on all Medicaid enrollees in fourteen southern states. Compared to other racial and ethnic groups, African American women tended to be younger, more likely to have a Cesarean section, to stay longer in the hospital and to incur higher Medicaid costs. African-American women were also more likely to experience preeclampsia, placental abruption, preterm birth, small birth size for gestational age, and fetal death/stillbirth. Eliminating racial disparities in adverse pregnancy outcomes (not counting infant costs), could generate Medicaid cost savings of $114 to $214 million per year in these 14 states. Despite having the same insurance coverage and meeting the same poverty guidelines for Medicaid eligibility, African American women have a higher rate of adverse pregnancy outcomes than White or Hispanic women. Racial disparities in adverse pregnancy outcomes not only represent potentially preventable human suffering, but also avoidable economic costs. There is a significant financial return-on-investment opportunity tied to eliminating racial disparities in birth outcomes. With the Affordable Care Act expansion of Medicaid coverage for the year 2014, Medicaid could be powerful public health tool for improving pregnancy outcomes.     

Self-reported exposure to pesticides and radiation related to pregnancy outcome--results from National Natality and Fetal Mortality Surveys

Although fetal development is known to be sensitive to environmental agents, relatively little epidemiologic research has addressed this concern. Effects on pregnancy outcome of self-reported parental exposure to pesticides and to radiation were examined using data from the National Natality and Fetal Mortality Surveys, large national probability samples of live births and stillbirths occurring in 1980. In case-control analyses, maternal exposure to pesticides at home or work was associated with increased risk of stillbirth (odds ratios (ORs) = 1.5-1.6). Paternal pesticide exposure was associated with stillbirth (ORs = 1.2-1.4) and delivery of small-for-gestational-age infants (ORs = 1.4-2.0). A small increased risk of stillbirth (OR = 1.3) was found in relation to either parent's reported exposure to radiation. In spite of limitations in the quality of exposure data and the possibility of biased recall related to pregnancy outcome, associations of reported pesticide exposure to either parent with risk of stillbirth and small-for-gestational-age infants warrant further evaluation.     

Determinants of perinatal and infant mortality in Italy.

Determinants of stillbirths, perinatal and infant mortality in Italy have been analyzed using information collected routinely by the Italian Central Institute of Statistics on more than 2,400,000 births and 33,000 infant deaths in the period 1980-1983. Individual records included data on maternal (i.e. age, education, obstetric history) and fetal characteristics (sex, birth weight, gestational week at birth). The Italian stillbirth, perinatal and infant (1st-365th day of life) mortality rates in the period considered were respectively 7.7/1000 births, 16.4/1000 births and 13.5/1000 livebirths. Perinatal and infant mortality was extremely elevated in the very-low-birth-weight category. About 90% of liverbirths weighing less than 1000 g died within the first year of life, but this fell to about 45% in babies weighing 1000-1499 g. Among other factors, stillbirth, perinatal and infant mortality rates were elevated among males, born to older women and in higher birth rank and multiple pregnancies. These findings persisted, although less markedly, after adjustment for weight. Mortality rates were about 50-70% higher in less educated women. This finding was not markedly changed after adjustment for birth weight and maternal age, suggesting that socio-economic factors are per se important determinants of perinatal and infant mortality in Italy.     

77例宫内死胎的相关危险因素分析

目的探讨77例宫内死胎的相关危险因素。方法回顾性分析2004~2013年清华大学第一附属医院收治的宫内死胎产妇的临床病历资料(病例组),并随机选取同期200例单胎活产分娩产妇病历资料(对照组),采用多因素Logistic回归分析宫内死胎的危险因素。结果单因素结果显示,高龄(30岁)、妊娠期高血压疾病、胎盘早剥、前置胎盘、脐带异常、无规律产检、羊水异常、胎儿发育异常的孕妇更易出现宫内死胎(P0.05);不同孕次、产次、流产史、妊娠期糖尿病的孕妇宫内死胎的发生率比较差异无统计学意义(P0.05);不同性别胎儿宫内死胎率比较差异无统计学意义(P0.05)。多因素Logistic回归分析结果显示,高龄(30岁)、妊娠期高血压疾病、胎盘早剥、前置胎盘、脐带异常、羊水异常、胎儿发育异常是宫内死胎的独立危险因素(OR分别为1.675、1.956、1.863、1.985、1.677、1.945、1.954,P均0.05);规律产检是保护因素(OR=0.542,P0.05)。结论高龄(30岁)、妊娠期高血压疾病、胎盘早剥、前置胎盘、脐带异常、羊水异常、胎儿发育异常是宫内死胎的独立危险因素,临床应重点关注高危人群,采取针对性措施进行干预。     

Unemployment and stillbirth risk among foreign-born and Spanish pregnant women in Spain, 2007–2010: a multilevel analysis study

We describe stillbirth and unemployment rates by autonomous region in Spain and analyse whether women who gave birth in regions with high unemployment rates were more likely to have a stillborn. We designed a multilevel population-based observational study of births from 2007 to 2010. We defined stillbirth as the outcome, individual maternal socioeconomic and pregnancy-related characteristics as covariates, and maternal autonomous region of residence as the contextual covariate. We used mixed-logistic regression models to account for differences across regions. In total, 1,920,235 singleton births and 5,560 stillbirths were included in the study. Women residing in autonomous regions with the highest rates of unemployment had a two-times-greater chance of delivering a stillborn (adjusted OR 2.60; 95 % CI 2.08–3.21). The region where women resided explained 14 % of the total individual differences in the risk of delivering a stillborn. The odds of stillbirth were 1.82 (95 % CI 1.62–2.05) times higher for African-born women than for Spanish-born women and 1.90 (95 % CI 1.68–2.15) times higher for women with low educational attainment than for women with higher education. In conclusion, regional disparities in stillbirth rates in Spain in the period 2007–2010 were mainly associated with mothers who had low levels of education, were African-born, and lived in regions with higher unemployment.     

Risk of stillbirth from occupational and residential exposures.

OBJECTIVES: To analyse the risk of stillbirth from 12 residential and occupational maternal exposures during pregnancy. METHODS: Stillbirths and neonatal deaths in 1984 within 24 hours of birth from 10 California counties were identified from death certificates. Controls were randomly selected from live births born in 1984 and frequency matched to cases by maternal age and county. Data sources included vital statistics and a self-administered postal questionnaire. Logistic regression and proportional hazards modelling were performed; the proportional hazards considered the truncated opportunity for exposure among cases. Special focus was given to two cause of deaths groups: congenital anomalies (12% of deaths) and complications of the placenta, cord, and membranes (37% of deaths). RESULTS: Occupational exposure to pesticides during the first two months of gestation was positively associated with stillbirths due to congenital anomalies (odds ratio (OR) 2.4, 95% confidence interval (95% CI) 1.0 to 5.9), and during the first and second trimesters with stillbirths due to all causes of death (risk ratios (RR) 1.3-1.4, 95% CI 1.0 to 1.7) and stillbirths due to complications of the placenta, cord, and membranes (RR 1.6-1.7, 95% CI 1.1 to 2.3). Occupational exposure to video display terminals in the third trimester was found to have a modest inverse association with stillbirths (RR 0.7, 95% CI 0.6, 0.9). Home pesticide exposure was positively associated with stillbirths due to congenital anomalies (OR 1.7, 95% CI 1.0 to 2.9). CONCLUSIONS: Occupational exposure to pesticides, especially during early pregnancy, had a clear positive association with stillbirths regardless of cause of death. Methodologically, this study of stillbirths is unique in its analysis of specific causes of death and use of time specific exposure windows.     

78例死胎高危因素临床分析

目的:探讨死胎发生的高危因素。方法:将2007年1月～2010年11月苏州大学附属第一人民医院住院分娩的死胎78例设为病例组,随机抽取同期住院分娩活产156例作为对照组,对两组18个社会及临床因素进行回顾性分析。结果:比较两组的高龄、职业、教育程度、产前检查、孕周、出生体重、胎数、产次、胎膜早破、胎盘早剥、胎儿畸形、母体合并症等指标,差异有统计学意义。Logistic回归分析表明无正规产前检查(OR=3.202,95%CI 3.074～3.548)、低出生体重(OR=0.998,95%CI 0.997～0.999)、无业(OR=1.279,95%CI 1.096～1.804)、胎儿畸形(OR=2.264,95%CI 2.102～2.573)、母体疾病(OR=4.608,95%CI 10.859～24.707)是发生死胎的高危因素。结论:必须加强产前检查,提高产前诊断水平,及时发现早期胎儿畸形,加强对高危孕妇的筛选及重点监护,积极治疗各种妊娠合并症及并发症,减少死胎的发生。     

Causes of stillbirths and early neonatal deaths: data from 7993 pregnancies in six developing countries

OBJECTIVE: To report stillbirth and early neonatal mortality and to quantify the relative importance of different primary obstetric causes of perinatal mortality in 171 perinatal deaths from 7993 pregnancies that ended after 28 weeks in nulliparous women. METHODS: A review of all stillbirths and early newborn deaths reported in the WHO calcium supplementation trial for the prevention of pre-eclampsia conducted at seven WHO collaborating centres in Argentina, Egypt, India, Peru, South Africa and Viet Nam. We used the Baird-Pattinson system to assign primary obstetric causes of death and classified causes of early neonatal death using the International classification of diseases and related health problems, Tenth revision (ICD-10). FINDINGS: Stillbirth rate was 12.5 per 1000 births and early neonatal mortality rate was 9.0 per 1000 live births. Spontaneous preterm delivery and hypertensive disorders were the most common obstetric events leading to perinatal deaths (28.7% and 23.6%, respectively). Prematurity was the main cause of early neonatal deaths (62%). CONCLUSIONS: Advancements in the care of premature infants and prevention of spontaneous preterm labour and hypertensive disorders of pregnancy could lead to a substantial decrease in perinatal mortality in hospital settings in developing countries.     

Interpregnancy Interval and Risk of Adverse Pregnancy Outcomes: A Register-Based Study of 328,577 Pregnancies in Denmark 1994–2010

Objectives To investigate the associations of interpregnancy interval (IPI) with miscarriage, stillbirth, preterm delivery and small for gestational age delivery. Methods The study population comprised all women who had a live birth and at least one subsequent pregnancy in Denmark during the period from 1994 to 2010 (N?=?328,577). Linear regression was used to estimate risk differences for miscarriage, stillbirth, preterm delivery and small for gestational age delivery according to IPI. Results The results were heterogeneous: the risk of miscarriage increased monotonically with the length of the IPI. Compared to women with IPIs of 18–23 months, women with IPIs of 0–5 months experienced 18.7 (13.1–24.2) fewer miscarriages per 1000 pregnancies, while women with IPIs of ≥?60 months experienced 28.7 (23.4–34.0) more miscarriages per 1000 pregnancies. We found that women with IPIs of ≥?60 months had 1.7 (0.4–3.0) more stillbirths per 1000 births compared to women with IPIs of 18–23 months. U-shaped associations were seen for preterm delivery and small for gestational age delivery with women with IPIs of 18–23 months experiencing the lowest risks of these outcomes. Conclusions for Practice The heterogeneity in associations between IPI and adverse pregnancy outcomes suggests that different mechanisms of action may be at play at various times in the antepartum period. While the finding for miscarriage suggests that fecundity is an important determinant for IPI, the findings for preterm delivery and small for gestational age delivery suggest the coexistence of the maternal depletion syndrome mechanism and the physiological regression mechanism and the finding for stillbirth speaks against a strict maternal depletion syndrome explanation.