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.     

Management of decreased fetal movements

Maternal perception of decreased fetal activity is a common complaint, and one of the most frequent causes of unplanned visits in pregnancy. No proposed definitions of decreased fetal movements have ever been proven to be superior to a subjective maternal perception in terms of identifying a population at risk. Women presenting with decreased fetal movements do have higher risk of stillbirth, fetal growth restriction, fetal distress, preterm birth, and other associated outcomes. Yet, little research has been conducted to identify optimal management, and no randomized controlled trials have been performed. The strong associations with adverse outcome suggest that adequate management should include the exclusion of both acute and chronic conditions associated with decreased fetal movements. We propose guidelines for management of decreased fetal movements that include both a nonstress test and an ultrasound scan and report findings in 3014 cases of decreased fetal movements.     

Events after Stillbirth in Relation to Maternal Depressive Symptoms: A Brief Report

ABSTRACT: Background: Actions taken after a stillbirth can affect long‐term psychological morbidity. Our objective was to study how infant bonding and maternal actions after stillbirth are associated with ensuing depressive symptoms. Methods: Using the population‐based Swedish Medical Birth Register, we identified all 380 Swedish‐speaking women who gave birth to singleton stillborn infants in Sweden in 1991. Of these, 314 (83%) completed a postal questionnaire 3 years after the stillbirth. Items included actions taken to bond with the baby and demographics. The association between care‐related factors and later maternal depressive symptoms was quantified using relative risks estimated using multivariable regression. Results: We observed an almost sevenfold increased risk of depressive symptoms for mothers who reported not being with their babies as long as they wished (adjusted risk ratio [RR] 6.9, 95% CI 2.4–19.8). Compared with women who became pregnant again within 6 months, those with no later pregnancy were at higher risk of depressive symptoms (adjusted RR 2.8, 95% CI 0.9–8.4). In addition, compared with women who experienced a stillbirth in their first pregnancy, stillbirth occurring with an infant who was third in the birth order was related to a twofold risk of elevated depressive symptoms (adjusted RR 2.2, 95% CI 0.8–6.4). Furthermore, stillbirth occurring in a fourth or later pregnancy was associated with an almost sevenfold risk of depressive symptomatology (adjusted RR 6.7, 95% CI 2.2–20.5). No evidence of an association was found between other care‐related actions and subsequent maternal depressive symptoms. Conclusions: Our results suggest that a mother being with the stillborn baby for as long as desired and the birth order of the stillbirth may influence her later depressive symptomatology. Compared with mothers who became pregnant again within 6 months, those who did not have a subsequent pregnancy were at higher risk of depressive symptoms at 3 years’ follow‐up. (BIRTH 35:2 June 2008)     

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.     

Prepregnancy obesity and fetal death: a study within the Danish National Birth Cohort

OBJECTIVE: To examine the association between high prepregnancy body mass index and fetal death, allowing for the effects of gestational age, weight gain, and maternal diseases in pregnancy. METHODS: Prepregnancy body mass index (BMI) and fetal death were examined in the Danish National Birth Cohort among 54,505 pregnant women who participated in a comprehensive interview during the second trimester. Pregnancy outcomes were obtained from registers and medical records. Cox regression analyses with delayed entry and time-dependent covariates were used to estimate the risk of fetal death. RESULTS: Compared with normal-weight women (18.5 < or = BMI < 25), the risks of fetal death among obese women (BMI > or = 30), expressed as adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were as follows: before week 14: 0.8 (0.5-1.4), weeks 14-19: 1.6 (1.0-2.5), weeks 20-27: 1.9 (1.1-3.3), weeks 28-36: 2.1 (1.0-4.4), weeks 37-39: 3.5 (1.9-6.4), and weeks 40+: 4.6 (1.6-13.4). Overweight women (25 < or = BMI < 30) also experienced a higher risk after 28 weeks, and especially after 40 weeks of gestation (HR 2.9, 95% CI 1.1-7.7). Analysis of stillbirth (fetal death at 28+ completed weeks of gestation) indicated that the effects were not due to obesity-related diseases in pregnancy, nor was weight gain associated with stillbirth. The increased risk of stillbirth among overweight and obese women was partly attributable to inadequate placental function (crude odds ratios 2.1, 95% CI 1.0-4.4, and 5.2, 95% CI 2.5-10.9, respectively). CONCLUSION: Prepregnancy obesity was associated with an increasing excess risk of fetal death with advancing gestation, and placental dysfunction may be a possible contributing factor.     

Maternal anxiety and fetal movement patterns in late pregnancy

Objective: To determine whether maternal anxiety affects fetal movement patterns in the third trimester of pregnancy.

Methods: The inclusion criteria were a state of good health and a singleton pregnancy between 36 and 40 weeks. Thirty healthy pregnant women were included. The Beck Anxiety Inventory (BA) questionnaire with 21 self-reported items validated for the Brazilian population was applied. The women were asked to record the number of minutes taken to perceive 10 fetal movements once a day for one week. Anxiety symptoms were rated as moderate or severe according to the BAI total score.

Results: The mean BAI score was 20.8 (SD?=?10.2) and the mean time to count 10 fetal movements was 24.3?min (SD?=?6.6?min). The BAI items significantly associated with moderate or severe maternal anxiety were numbness or tingling, fear of the worst happening, terrified, feeling of choking, fear of losing control and fear of dying. There was a statistically significant negative correlation between the total BAI score and the mean time of 10 perceived fetal movements (p?<?0.0001; rho?=??0.70; 95% CI for rho ?0.84 to ?0.45).

Conclusions: Maternal anxiety seems to affect fetal movement patterns in late pregnancy and is associated with the mother’s increased perception of fetal activity.     

Pregnancy Outcome After Previous Stillbirth Resulting from Causes Other Than Maternal Conditions and Fetal Abnormalities

Background: An adequate fetomaternal circulatory system may be compromised by a variety of disturbances leading to stillbirth. The purpose of this study was to assess subsequent pregnancy outcome in women with a history of stillbirth as a result of causes other than maternal conditions and fetal abnormalities. Methods: Ninety‐two deliveries after stillbirth were identified among 11,910 deliveries of parous women recorded in the birth registry at Kuopio, Finland. Using logistic regression, pregnancy outcome measures were compared with those of a parous healthy obstetric population (n= 11,818). Results: Women with a history of stillbirth as a result of causes other than maternal conditions and fetal abnormalities were older than their unaffected controls (32.4 yr vs 30.3 yr). Stillbirth in an earlier pregnancy was associated with a significantly higher (p < 0.001) frequency of placental abruption in subsequent pregnancy (5.4% vs 0.7%). A history of stillbirth was predictive of preterm delivery (OR = 2.25) and low‐birthweight infants (OR = 2.70). No recurrence was reported. Conclusions: Pregnancy with a history of stillbirth as a result of causes other than maternal conditions and fetal abnormalities is a moderate risk state, with prematurity and low‐birthweight rates somewhat higher than those in the general population. The overall probability of a favorable outcome is good. These findings may be useful in counseling pregnant women with a history of stillbirth.     

Quitting Smoking During Early Versus Late Pregnancy: The Risk of Preeclampsia and Adverse Birth Outcomes

ObjectiveTo examine the impact of women’s quitting smoking during early and late pregnancy on their risk of preeclampsia and on birth outcomes.MethodsWe analyzed data from a case–control study of 86 preeclamptic women and 239 controls at three hospitals in Quebec between January 2003 and March 2006.ResultsCompared with never having smoked, early smoking cessation, i.e., quitting before 20 weeks’ gestation, was not associated with a reduced risk of preeclampsia (adjusted OR 1.03; 95% CI 0.42–2.60). Both late smoking cessation (quitting after 20 weeks of gestation) and persistent smoking (smoking before and during pregnancy) were associated with a non-significant reduction in the risk of preeclampsia (aOR 0.78; 95% CI 0.12–5.02 for late quitting and aOR 0.62; 95% CI 0.16–2.37 for persistent smoking). However, persistent smoking was associated with an increased risk of other adverse pregnancy outcomes, such as low birth weight (aOR 10.2; 95% CI 2.49–41.8) and preterm birth (aOR 3.59; 95% CI 1.06–12.1).ConclusionAlthough late quitting and persistent smoking may be associated with a decreased risk of preeclampsia, the benefit of early smoking cessation on pregnancy outcome is evident.     

Stillbirth in cases of severe acute maternal morbidity

ObjectiveTo determine the incidence and correlates of stillbirths among women with severe acute maternal morbidity (SAMM).MethodsIn an observational study of 728 women who had SAMM between January 2007 and December 2010 at a referral tertiary health facility in Benin, Nigeria, the incidence of stillbirth, and the clinical and demographic correlates of stillbirth were evaluated.ResultsThe rate of stillbirth among women with SAMM was 210 per 1000 deliveries. The rate among women who had uterine rupture (643 per 1000 deliveries) far exceeded other cause-specific rates of stillbirth. Unbooked status (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.3–3.8), low maternal education (OR, 2.1; 95% CI, 1.2–4.0), vaginal delivery (OR, 8.1; 95% CI, 5.1–13.0), and maternal comorbidity (OR, 12.9; 95% CI, 6.2–26.9) were factors associated with stillbirth after adjusting for confounding variables.ConclusionIn Nigeria, SAMM was found to be associated with an unacceptably high rate of stillbirth. Strategies to improve fetal surveillance among women with SAMM are necessary to address the excessively high incidence of stillbirth among these patients.     

A kick from within--fetal movement counting and the cancelled progress in antenatal care

Interest for maternal fetal movement counting as a method of screening for fetal well-being boomed during the 1970's and 1980's. Several reports demonstrated that the introduction of counting charts significantly reduced stillbirth rates. However, in 1989, a large study appeared in The Lancet that annihilated research in this field by deeming charts ineffective. In retrospect, it seems evidence was lacking. This review revisits the subject of the significance of fetal movement counting in predicting outcome and reducing stillbirth rates. A structured search was performed to identify studies relating to pregnancy outcome and its association with maternal perception of fetal movements. Suspected preliminary or redundant material was excluded. Only publications from Western countries dating from after 1970 were included. Twenty-four studies were identified. Available data demonstrate that reduced fetal movements are associated with adverse pregnancy outcome, both in high and low risk pregnancies. Increased vigilance towards maternal perception of movements (e.g. by performing movement counting studies) reduces stillbirth rates, in particular stillbirths deemed avoidable. While screening for fetal well-being by maternal fetal movement counting can reduce fetal mortality rates, a resurrection in research activity is urgently needed to optimize its benefits.     

Factors associated with delivery at or after 28 weeks gestation in women with bulging fetal membranes before 26 weeks gestation

Objective: To elucidate the factors that contribute to prolonged pregnancy and promote neonate survival in women with bulging fetal membranes.

Methods: A database was reviewed to identify women with singleton pregnancies who underwent amniocentesis on admission to determine amniotic fluid neutrophil elastase levels before 26?+?0 weeks gestation between July 2001 and January 2015. Following delivery, the placentas of these patients were examined for histologic chorioamnionitis.

Results: Ninety-seven women delivered before 28 weeks gestation, and 117 women delivered at or after 28 weeks gestation. Rescue cerclage performed via the McDonald procedure (adjusted odds ratio [aOR]: 3.78; 95% confidence interval [CI]: 1.35–11.80) was associated with a higher likelihood of reaching at least 28 weeks gestation before delivery, whereas protruding membranes (aOR: 0.38; 95% CI: 0.18–0.78), elevated amniotic neutrophil elastase levels (≥0.15?μg/ml) (aOR, 0.41; 95% CI: 0.20–0.82) and elevated peripheral C-reactive protein levels (≥0.4?mg/dl) (aOR: 0.34; 95% CI: 0.180.65) were associated with a significantly reduced likelihood of reaching this gestational age before delivery. Among women who underwent rescue cerclage, amniorrhexis was associated with a negative prognosis (aOR: 0.18; 95% CI: 0.05–0.51).

Conclusions: Intra-amniotic inflammation, protrusion of fetal membranes and amniorrhexis are factors that may prevent pregnancy prolongation. Rescue cerclage improves pregnancy outcomes.     

Perinatal outcomes with intrahepatic cholestasis of pregnancy in twin pregnancies

Objective: To describe perinatal outcomes of twin pregnancies complicated by intrahepatic cholestasis of pregnancy (ICP).

Methods: We conducted a retrospective cohort study of women delivered at a large tertiary obstetric center in Shanghai, China from January 2006 to May 2014. Delivery data were abstracted from medical records of all twin gestations delivered at the hospital.

Results: A total of 129/1922(6.7%) twin and 1190/92?273 singleton (1.3%) pregnancies were complicated by ICP. An increased risk of stillbirth among twin pregnancies was observed (3.9% and 0.8% in the ICP and non-ICP groups, respectively; aOR 5.75, 95% CI 2.00–16.6). Stillbirths with ICP and twins occurred between 33 and 35 weeks gestation compared to 36–38 weeks gestation among singletons. ICP in twins was also associated with an increased risk of preterm birth (<37 weeks) with an aOR of 4.17 (95% CI 2.47–7.04) and an aOR of 1.89 (95% CI 1.26–2.85) for delivery <35 weeks. Twin pregnancies complicated by ICP also had increased meconium staining of amniotic fluid and lower birth weight.

Conclusions: Twin pregnancies with ICP have significantly increased risks of adverse perinatal outcomes including stillbirth and preterm birth. Stillbirth occurs at an earlier gestational age in twin gestation compared to singletons, suggesting that earlier scheduled delivery should be considered in these women.     

Maternal perception of fetal movements in late pregnancy is affected by type and duration of fetal movement

Objective: A reduction in fetal movements has been proposed to identify pregnancies at risk of stillbirth. The utility of this approach is limited by variability in maternal perception of fetal movements. We aimed to determine the proportion of fetal movements observed by ultrasound that were maternally perceived and identify factors that affected maternal perception.

Method: During 30-min recordings, women (n = 21) depressed a trigger upon perception of a fetal movement, while an ultrasound operator recorded observed movements according to the fetal parts involved.

Results: Women perceived between 2.4% and 81.0% (median 44.8%) of movements observed on scan. Synchronous movement of the fetal trunk and limbs was more likely to be recognized than either part in isolation (60.5% versus 37.5% and 30%, respectively). The ultrasound operator judged the fetus to be moving for a significantly greater proportion of the time than mothers (median 1.5% of total recording time versus 0.7%). There was no significant relationship between the ability to perceive fetal activity and placental site, parity, amniotic fluid index or maternal body mass index.

Conclusion: Variations in maternal perception of fetal movements may affect detection of a clinically significant reduction in fetal movements for some women.     

Fetal morbidity and mortality after acute human parvovirus B19 infection in pregnancy: prospective evaluation of 1018 cases

OBJECTIVE: To determine more precisely the incidence of fetal complications following maternal parvovirus B19 infection at various gestational ages. METHODS: An observational prospective study of 1018 pregnant women whose acute B19 infection was serologically confirmed in our laboratory. RESULTS: The observed rate of fetal death throughout pregnancy was 6.3% (64/1018) (95% confidence interval [CI]: 4.9, 8.0). The fetal death rate for those infected within the first 20 weeks of gestation (WG) was 64/579 (11.0%). Fetal death was only observed when maternal B19 infection occurred before the completed 20 WG. The observed stillbirth proportion was 0.6% (6/960). Three of six stillbirth cases presented with fetal hydrops. The overall risk of hydrops fetalis was 3.9% (40/1018) (95% CI: 2.8, 5.3). Three of 17 cases with non-severe hydrops and 13 of 23 cases with severe hydrops received intrauterine transfusion(s). The proportion of fetuses with severe hydrops that survived following fetal transfusions was 11/13 (84.6%). All of the non-transfused fetuses with severe hydrops died. CONCLUSION: Our data demonstrate a relevant B19-associated risk of fetal death, which is largely confined to maternal B19 infection in the first 20 WG. Timely intrauterine transfusion of fetuses with severe hydrops fetalis reduces the risk of fetal death. Parvovirus B19-associated stillbirth without hydropic presentation is not a common finding.     

Evaluation of maternal perception of sound-provoked fetal movement as a test of antenatal fetal health

Maternal perception of sound-provoked fetal movement was correlated with the results of nonstress cardiotocography in 1097 women with obstetric or medical antenatal risk factors. Ninety-two percent of the mothers felt fetal movements with the stimulus; all but three had a reactive non-stress test (NST). These three women were taking multiple antihypertensive drugs and were less than 33 weeks' gestation. Of 88 patients with no maternal perception of sound-provoked fetal movement, ten had nonreactive NSTs. Ultrasound confirmed the absence of fetal movement to the stimulus. The outcome in nine of these ten cases suggested some evidence of fetal compromise. Maternal perception of sound-provoked fetal movement correlated well with the results of the NST; the sensitivity (76.9%), specificity (92.8%), and negative predictive value (99.7%) were all high, although the positive predictive value was only 11.4%. Maternal perception of sound-provoked fetal movement may suffice as an inexpensive and simple method of evaluating antenatal fetal well-being in risk situations. When the mother is doubtful or does not feel the sound-provoked fetal movement, NST is indicated to evaluate the fetal health.     

Evaluation of fetal movements with ultrasonic Doppler fetal actograph

Fetal movements in each trimester were recorded objectively and continuously with an ultrasonic Doppler actograph that enables simultaneous tracing of fetal heart rate (FHR) and fetal movement (FM). The record with this method was compared with those of the ultrasonic B-mode and M-mode respectively. The onset of FM signal bursts and FHR acceleration was nearly synchronous and the transitory FHR increase associated with FM signal bursts showed a linear amplitude increment along with the progress of gestation. Fetal hiccup movements were recorded from 24 weeks of gestation and lasted between 4.3 minutes and 17 minutes with a rate of 25 to 28 per minute. No FHR acceleration was recognized in such movements. Maternal perception was 67.7% on average of FM signal bursts. Fetal movements in early pregnancy were detected in the 11th week of gestation (CRL 54 mm). Long-term recording of fetal movements was carried out between 9:30 and 17:00 and the alternation of active and resting phases was investigated. The resting phase lasted 20 minutes on average, (range, 10 to 36 minutes). The fetal activity was not influenced by the maternal food intake. It is clinically significant to evaluate the change in fetal movements objectively and continuously.     

Maternal smoking and preeclampsia

OBJECTIVE: To study the relationship between maternal smoking and preeclampsia and whether this association differs between primiparous and multiparous women. STUDY DESIGN: We conducted a population-based, retrospective, cohort study of 58,216 singleton pregnancies from northern and central Alberta, Canada, between 1995 and 1997. Multivariate logistic regression was used to control for maternal alcohol consumption, drug dependence, maternal age, maternal weight, prior intrauterine growth restriction and other confounders. RESULTS: Maternal smoking was associated with a significantly reduced overall risk of preeclampsia (adjusted odds ratio [aOR]: .61; 95% confidence interval [CI]: .50-.75; P < .01). Stratified analyses showed that in primiparous pregnancies, maternal smoking was associated with a significantly decreased risk (aOR: .63; 95% CI: .50-.80; P < .01); in multiparous women, maternal smoking was not associated with a statistically significant decreased risk of preeclampsia (aOR: 0.72; 95% CI: .51-1.02; P > .05). CONCLUSION: Maternal smoking is protective against preeclampsia. Understanding the underlying biologic mechanisms of this protective effect may advance our knowledge of the pathogenesis of preeclampsia.     

胎动监测意义的再评估

胎动计数是常用的胎儿产前监测方法之一，胎动正常模式的改变预示着胎儿宫内状态异常。研究发现，胎动减少常是胎儿窘迫的首要征象，与死胎、胎盘功能不全、胎儿生长受限等不良妊娠结局相关；妊娠32周后胎动增加是正常的胎动规律，但单次过度运动与死胎有关。临床上通过孕妇自数胎动的方式初步评估胎儿宫内安危以便早期发现胎儿异常，减少不良妊娠结局的发生，这种方法具有经济、方便、简单、能反映部分问题的特点，但是较为主观，孕妇个体感受的胎动差异较大。     

The influence of maternal smoking habits on the risk of subsequent stillbirth: is there a causal relation?

Objective  Maternal smoking has previously been associated with risk of stillbirth. If women who quit smoking reduce their risk of stillbirth, the hypothesis of a causal association would be supported.
Design  Prospective cohort study.
Setting  Nationwide study in Sweden.
Population  All primiparous women who delivered their first and second consecutive single births between 1983 and 2001, giving a total number of 526 691 women.
Method  A population-based Swedish study with data from the Medical Birth Registry, the Immigration Registry and the Education Registry. Logistic regression analyses were used to estimate odds ratios, using 95% confidence intervals.
Main outcome measure  Stillbirth in the second pregnancy.
Results  Compared with nonsmokers in both pregnancies, women who smoked during the first pregnancy but not during the second do not have an increased risk of stillbirth (OR 1.02; 95% CI 0.79–1.30), while corresponding risk among women who smoked during both pregnancies was 1.35 (95% CI 1.15–1.58).
Conclusion  The result supports that maternal smoking during pregnancy is causally associated with stillbirth risk. Smoking is a preventable cause of stillbirth, and smoking interventions is an important issue in antenatal care.     

Second-trimester maternal serum alpha-fetoprotein and risk of adverse pregnancy outcome(1)

OBJECTIVE: To determine the risk of adverse pregnancy outcome by maternal serum alpha-fetoprotein (MSAFP) level. METHODS: We followed 77,149 pregnant women and their infants from MSAFP screening in the 15th to 20th week of gestation until 1 year after birth. Information on pregnancy outcome was obtained from national registries. The relative risks (RRs) and 95% confidence intervals (CIs) for adverse pregnancy outcome were estimated according to the level of MSAFP, with adjustment for confounders. RESULTS: A total of 638 pregnancies resulted in spontaneous abortion, 289 in stillbirth, and 437 in infant death. Compared with women with MSAFP levels at 0.75-1.24 multiples of the median (MoM), those with MSAFP levels greater than or equal to 2.5 MoM had an increased risk of spontaneous abortion (RR 12.5; 95% CI 9.7, 16.1), preterm birth (RR 4.8; 95% CI 4.1, 5.5), small for gestational age (RR 2.8; 95% CI 2.4, 3.2), low birth weight (RR 5.8; 95% CI 5.0, 6.6), and infant death (RR 1.9; 95% CI 1.2, 2.8). Women with MSAFP levels below 0.25 MoM had an increased risk of spontaneous abortion (RR 15.1; 95% CI 9.3, 24.8), preterm birth (RR 2.2; 95% CI 1.3, 3.8), and stillbirth (RR 4.0; 95% CI 1.0, 16.0); those with levels less than 0.5 MoM had an increased risk of infant death (RR 1.9; 95% CI 1.2, 3.0). The increased risk of infant death remained after the subtraction of recognized conditions associated with extreme MSAFP values. CONCLUSION: Pregnant women with extreme MSAFP values in the second trimester have an increased risk of fetal and infant deaths. Obstet Gynecol 2001;97:277-82.