Preterm Live Births Research Articles

Epidemiology of preterm birth in Omdurman maternity hospital, Sudan

Objective. To investigate the prevalence and to identify risk factors for live singleton preterm birth in Omdurman Maternity hospital, Sudan.Methods. Case–control study. Odds ratios were adjusted for the confounding factors using multiple logistic regression models.Results. Among 3240 live birth at maternity hospital during the 3 months period of the study, 126 (3.8%) were a live preterm birth. About 99 live preterm births at a mean (SD) of 32.7 (2.2) gestational weeks were included in the final analyses. About 80 (81.0%) of these 99 preterm births were spontaneous preterm births and the rest 19 (19.0%) were medically indicated preterm births. Univariate and Multivariate analyses showed that those women who had history of miscarriage, preterm birth, cesarean delivery, dental maneuver, and vaginal bleeding in the index pregnancy, both low body mass index (BMI) (<25) and high BMI (>30) and those women who had short interpregancy interval were at higher risk for preterm birth.Conclusions. The study showed that spontaneous preterm birth predominates in this setting. Preterm birth has a tendency to recur. Infections (periodontal) and nutrition were the risk factors for preterm birth. More research is needed especially in the area of nutrition and oral hygiene.

Prior Adverse Pregnancy Outcome and the Risk of Stillbirth

To estimate whether a history of fetal growth restriction, abruptio placentae, preeclampsia, or live preterm birth is associated with excess risk of stillbirth in a subsequent pregnancy. We also estimated the maternal and paternal contributions to such effects. This was a population-based cohort study from 1967 to 2005. Pairs of first and second, second and third, third and fourth, and fourth and fifth births were identified among all births from the Medical Birth Registry of Norway; 747,221 pairs with the same parents, 51,708 with the same mother and different father, and 65,602 with the same father and different mother. The associations of gestational age categories (22-27, 28-32, 33-36, and at or above 37 weeks), small for gestational age (SGA), preeclampsia, and abruptio placenta in the first pregnancy with stillbirth and late abortion in the second were assessed by odds ratios (ORs) obtained by logistic regression. The baseline rate of stillbirth during the study period was 1.0% of all births from 16 weeks of gestation. After births with gestational age 22-27, 28-32, and 33-36 weeks of gestation, stillbirth was six, three and two times more likely to occur than after a term birth (OR 5.7, 95% confidence interval [CI] 4.2-7.6; OR 2.6, 95% CI 2.1-3.3; and OR 1.7, 95% CI 1.5-1.9, respectively). Odds ratios of stillbirth subsequent to pregnancies with SGA, preeclampsia, and abruptio placentae were 1.7 (95% CI 1.6-1.9), 1.6 (95% CI 1.5-1.9), and 2.8 (95% CI 2.2-3.5), respectively, and increased with severity of the conditions. Gestational age below 33 weeks with preeclampsia or SGA carried 6-9 and 6-13-fold effects on later stillbirth, respectively. Men who fathered a pregnancy with preterm preeclampsia were significantly more likely to father a stillbirth in another woman (OR 2.4, 95% CI 1.1-5.5). Live preterm birth, fetal growth restriction, preeclampsia, and abruptio placenta are strongly associated with later stillbirth. II.

Outcomes at Age 2 Years of Infants < 28 Weeks' Gestational Age Born in Victoria in 2005

To determine the survival rates and neurosensory outcomes of infants born at gestational age 22-27 weeks in the state of Victoria in 2005 and compare theses data with those for similar infants born in the 1990s. This was a population-based study of all extremely preterm (22-27 weeks' gestational age) live births in Victoria in 2005 free of lethal anomalies and randomly selected term controls. Survival and quality-adjusted survival rates at age 2 years were determined relative to the controls, and results were compared with regional extremely preterm cohorts born in 1991-92 and 1997. Of 270 very preterm live births in 2005, 172 (63.7%) survived to 2 years, not significantly different from the survival rate of 69.6% for those born in 1997. Rates of severe developmental delay and severe disability were lower than in the very preterm survivors born in 1997. Quality-adjusted survival rates in the extremely preterm cohorts rose from 42.1% in 1991-92 to 55.1% in 1997, but did not increase in 2005 (53.4%). Survival rates for infants born at 22-27 weeks' gestational age have not increased since the late 1990s, but the neurosensory outcome in survivors has improved.

Systemic Immune Responses in Pregnancy and Periodontitis: Relationship to Pregnancy Outcomes in the Obstetrics and Periodontal Therapy (OPT) Study

Our previous studies reported on the obstetric, periodontal, and microbiologic outcomes of women participating in the Obstetrics and Periodontal Therapy (OPT) Study. This article describes the systemic antibody responses to selected periodontal bacteria in the same patients. Serum samples, obtained from pregnant women at baseline (13 to 16 weeks; 6 days of gestation) and 29 to 32 weeks, were analyzed by enzyme-linked immunosorbent assay for serum immunoglobulin G (IgG) antibody to Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Campylobacter rectus, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia (previously T. forsythensis), and Treponema denticola. At baseline, women who delivered live preterm infants had significantly lower total serum levels of IgG antibody to the panel of periodontal pathogens (P = 0.0018), to P. gingivalis (P = 0.0013), and to F. nucleatum (P = 0.0200) than women who delivered at term. These differences were not significant at 29 to 32 weeks. Changes in IgG levels between baseline and 29 to 32 weeks were not associated with preterm birth when adjusted for treatment group, clinical center, race, or age. In addition, delivery of low birth weight infants was not associated with levels of antibody at baseline or with antibody changes during pregnancy. Live preterm birth is associated with decreased levels of IgG antibody to periodontal pathogens in women with periodontitis when assessed during the second trimester. Changes in IgG antibody during pregnancy are not associated with birth outcomes.

Does Continuous Use of Metformin Throughout Pregnancy Improve Pregnancy Outcomes in Women With Polycystic Ovarian Syndrome?

Aim: Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies in women of reproductive age. It is associated with hyperinsulinemia and insulin resistance which is further aggravated during pregnancy. This mechanism has a pivotal role in the development of various complications during pregnancy. In the past few years, metformin, an insulin sensitizer, has been extensively evaluated for induction of ovulation. Its therapeutic use during pregnancy is, however, a recent strategy and is a debatable issue. At present, evidence is inadequate to support the long-term use of insulin-sensitizing agents during pregnancy. It is a challenge for both clinicians and researchers to provide good evidence of the safety of metformin for long-term use and during pregnancy. This study aimed to evaluate pregnancy outcomes in women with PCOS who conceived while on metformin treatment, and continued the medication for a variable length of time during pregnancy. Methods: This case-control study was conducted from January 2005 to December 2006 at the antenatal clinics of the Department of Obstetrics and Gynecology, Aga Khan University, Karachi, Pakistan. The sample included 137 infertile women with PCOS; of these, 105 conceived while taking metformin (cases), while 32 conceived spontaneously without metformin (controls). Outcomes were measured in three groups of cases which were formed according to the duration of use of metformin during pregnancy. Comparison was made between these groups and women with PCOS who conceived spontaneously. Results: All 137 women in this study had a confirmed diagnosis of PCOS (Rotterdam criteria). These women were followed up during their course of pregnancy; data forms were completed once they had delivered. Cases were divided into three groups: group A, 40 women who stopped metformin between 4–16 weeks of pregnancy; group B, 20 women who received metformin up until 32 weeks of gestation; and group C; 45 women who continued metformin throughout pregnancy. All the groups were matched by age, height and weight. Comparison was in terms of early and late pregnancy complications, intrauterine growth restriction and live birth rates. In groups A, B and C the rate of pregnancy-induced hypertension/pre-eclampsia was 43.7%, 33% and 13.9% respectively (P < 0.020). Rates of gestational diabetes requiring insulin treatment in groups A and B were 18.7% and 33.3% compared to 2.5% in group C (P < 0.004). The rate of intrauterine growth restriction was significantly low in group C: 2.5% compared to 19.2% and 16.6% in groups A and B respectively (P < 0.046). Frequency of preterm labor and live birth rate was significantly better in group C compared to groups A and B. Overall rate of miscarriages was 7.8%. Controls were comparable to group A in terms of early and late pregnancy complications. Conclusion: In women with PCOS, continuous use of metformin during pregnancy significantly reduced the rate of miscarriage, gestational diabetes requiring insulin treatment and fetal growth restriction. No congenital anomaly, intrauterine death or stillbirth was reported in this study.

Does continuous use of metformin throughout pregnancy improve pregnancy outcomes in women with polycystic ovarian syndrome?

Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies in women of reproductive age. It is associated with hyperinsulinemia and insulin resistance which is further aggravated during pregnancy. This mechanism has a pivotal role in the development of various complications during pregnancy. In the past few years, metformin, an insulin sensitizer, has been extensively evaluated for induction of ovulation. Its therapeutic use during pregnancy is, however, a recent strategy and is a debatable issue. At present, evidence is inadequate to support the long-term use of insulin-sensitizing agents during pregnancy. It is a challenge for both clinicians and researchers to provide good evidence of the safety of metformin for long-term use and during pregnancy. This study aimed to evaluate pregnancy outcomes in women with PCOS who conceived while on metformin treatment, and continued the medication for a variable length of time during pregnancy. This case-control study was conducted from January 2005 to December 2006 at the antenatal clinics of the Department of Obstetrics and Gynecology, Aga Khan University, Karachi, Pakistan. The sample included 137 infertile women with PCOS; of these, 105 conceived while taking metformin (cases), while 32 conceived spontaneously without metformin (controls). Outcomes were measured in three groups of cases which were formed according to the duration of use of metformin during pregnancy. Comparison was made between these groups and women with PCOS who conceived spontaneously. All 137 women in this study had a confirmed diagnosis of PCOS (Rotterdam criteria). These women were followed up during their course of pregnancy; data forms were completed once they had delivered. Cases were divided into three groups: group A, 40 women who stopped metformin between 4-16 weeks of pregnancy; group B, 20 women who received metformin up until 32 weeks of gestation; and group C; 45 women who continued metformin throughout pregnancy. All the groups were matched by age, height and weight. Comparison was in terms of early and late pregnancy complications, intrauterine growth restriction and live birth rates. In groups A, B and C the rate of pregnancy-induced hypertension/pre-eclampsia was 43.7%, 33% and 13.9% respectively (P<0.020). Rates of gestational diabetes requiring insulin treatment in groups A and B were 18.7% and 33.3% compared to 2.5% in group C (P<0.004). The rate of intrauterine growth restriction was significantly low in group C: 2.5% compared to 19.2% and 16.6% in groups A and B respectively (P<0.046). Frequency of preterm labor and live birth rate was significantly better in group C compared to groups A and B. Overall rate of miscarriages was 7.8%. Controls were comparable to group A in terms of early and late pregnancy complications. In women with PCOS, continuous use of metformin during pregnancy significantly reduced the rate of miscarriage, gestational diabetes requiring insulin treatment and fetal growth restriction. No congenital anomaly, intrauterine death or stillbirth was reported in this study.

Maternal unemployment: an indicator of spontaneous preterm delivery risk

The aim of this study was to assess the association between maternal employment and preterm delivery. A nationwide case-control study was conducted in 25 Portuguese public maternities. During a 4-month period, 769 consecutive single spontaneous preterm (<37 gestation weeks) live births and 1,053 term singleton babies born immediately after each preterm, were evaluated. Information was obtained by attending physicians using a questionnaire, with special emphasis on maternal work characterization. Logistic regression odds ratios (OR) were adjusted for maternal age, marital status, education and obstetrical characteristics. Women entering pregnancy while unemployed presented a significantly increased risk of spontaneous preterm delivery (OR=1.5; 95% confidence interval (CI) 1.18-1.88). Weekly duration of work (<40 versus >or=40 h) had no significant effect on the occurrence of spontaneous preterm (OR=1.2; 95% CI 0.88-1.54). Unemployed women presented a significant increase in the risk of preterm delivery.

Grande prématurité : faut-il s’intéresser à la corpulence maternelle ?

Link between maternal body mass index (BMI) and pregnancy outcome is not clear. To appreciate the impact of prepregnancy maternal BMI on very preterm birth (22-32 gestation's weeks). To assess how maternal BMI does explain the mechanism of very preterm birth among live births. Population-based study, including each mother with a live or stillborn baby was included in a geographically defined (Poitou-Charentes and Franche-comté, France) case-control study in 2004 to 2006. Leanness (BMI<18.5kg/m(2)) and overweight and obesity (BMI> or =25kg/m(2)) were defined according to World Health Organization's standards. Statistical analysis consisted in a polynomial regression on 832 mothers of very preterm babies and 431 mothers of full-term babies, taking account for confounders as maternal age, birth country, educational level, maternal work and smoking during the pregnancy. Leanness is a risk factor for very preterm live birth (aOR=1.73 [1.12-2.68]), overweight is a risk factor for stillbirth. (aOR=1.71 [1.03-2.84]). Among mothers of live born babies, leanness is a risk factor for spontaneous preterm birth (aOR=2.12 [1.20-3.74]), whereas overweight is a risk factor for very preterm birth on medical decision due to gestational hypertension (aOR=2.85 [1.80-4.52]). Morbid maternal stoutness before pregnancy is a complex risk factor for very preterm delivery. Women and couples should be informed and practitioners should be aware in order to prevent and manage this pathological status.

Termination of pregnancy among very preterm births and its impact on very preterm mortality: results from ten European population‐based cohorts in the MOSAIC study

To study the impact of terminations of pregnancy (TOP) on very preterm mortality in Europe. European prospective population-based cohort study. Ten regions from nine European countries participating in the MOSAIC (Models of OrganiSing Access to Intensive Care for very preterm babies) study. These regions had different policies on screening for congenital anomalies (CAs) and on pregnancy termination. Births 22-31 weeks gestational age. The analysis compares the proportion of TOP among very preterm births and assesses differences in mortality between the regions. Pregnancy outcomes (termination, antepartum death, intrapartum death and live birth) and reasons for termination, presence of CAs and causes of death for stillbirths and live births in 2003. Pregnancy terminations constituted between 1 and 21.5% of all very preterm births and between 4 and 53% of stillbirths. Most terminations were for CAs, although some were for obstetric indications (severe pre-eclampsia, growth restriction, premature rupture of membranes). TOP contributed substantially to overall fetal mortality rates in the two regions with late second-trimester screening. There was no clear association between policies governing screening and pregnancy termination and the proportion of CAs among stillbirths and live births, except in Poland, where neonatal deaths associated with CAs were more frequent, reflecting restrictive pregnancy termination policies. Proportions of TOP among very preterm births varied widely between European regions. Information on terminations should be reported when very preterm live births and stillbirths are compared internationally since national policies related to screening for CAs and the legality and timing of medical terminations differ.

Neonatal Mortality and Morbidity Rates in Late Preterm Births Compared With Births at Term

To analyze neonatal mortality and morbidity rates at 34, 35, and 36 weeks of gestation compared with births at term over the past 18 years at our hospital and to estimate the magnitude of increased risk associated with late preterm births compared with births later in gestation. We performed a retrospective cohort study of births at our hospital over the past 18 years. The study included all liveborn singleton infants between 34 and 40 weeks of gestation and without anomalies that were delivered to women who received prenatal care in our hospital system. Neonatal outcomes for late preterm births were compared with those for infants delivered at 39 weeks. Late preterm singleton live births constituted approximately 9% of all deliveries at our hospital and accounted for 76% of all preterm births. Late preterm neonatal mortality rates per 1,000 live births were 1.1, 1.5, and 0.5 at 34, 35, and 36 weeks, respectively, compared with 0.2 at 39 weeks (P<.001). Neonatal morbidity was significantly increased at 34, 35, and 36 weeks, including ventilator-treated respiratory distress, transient tachypnea, grades 1 or 2 intraventricular hemorrhage, sepsis work-ups, culture-proven sepsis, phototherapy for hyperbilirubinemia, and intubation in the delivery room. Approximately 80% of late preterm births were attributed to idiopathic preterm labor or ruptured membranes and 20% to obstetric complications. Late preterm births are common and associated with significantly increased neonatal mortality and morbidity compared with births at 39 weeks. Preterm labor was the most common cause (45%) for late preterm births. II.

Social inequalities in preterm birth in Scotland 1980–2003: findings from an area‐based measure of deprivation

The preterm birth rate in Scotland has been increasing in recent years. Although preterm birth rates show a social gradient, it is unclear how this gradient has been affected by the overall increase. We examined time trends in singleton live preterm birth rates in relation to area-based socio-economic indicators. Population-based retrospective cohort study. Scotland. All singleton live births delivered in Scottish hospitals between 1980 and 2003 (n= 1 423 993). Singleton live preterm birth rates in each deprivation quintile were derived. Subgroup analyses of those born moderately preterm (32-36 weeks), very preterm (28-31 weeks) and extremely preterm (24-27 weeks) were performed. The rate of singleton live preterm births increased from 49.7 per 1000 live births in the 5-year period 1980-84 to 56.1 per 1000 in the 4-year period 2000-03, a relative increase of 12.9%. A marked social gradient was apparent at all time periods: relative indices of inequality were 1.63 (95% CI 1.38-1.92) in 1980-84 and 1.55 (1.44-1.66) in 2000-03. Similar social gradients existed for all gestational age subgroups. Smoking status at first antenatal contact and increased obstetric intervention, possibly reflecting improvements in fetal monitoring and neonatal care, appeared to explain some but not all the social gradient. Social inequalities in preterm birth were apparent in Scotland between 1980 and 2003. In addition to helping pregnant women to stop smoking, other means to reduce social inequalities are required.

Spontaneous preterm birth of liveborn infants in women at low risk in Australia over 10 years: a population‐based study

To describe a 10-year trend in preterm birth. Population-based study. Australia. All women who gave birth during 1994-03. The proportion of spontaneous preterm births (greater than or equal to 22 weeks of gestation and less than 37 completed weeks of gestation) was calculated by dividing the number of women who had a live spontaneous preterm birth (excluding elective caesarean section and induction of labour) by the total number of women who had a live birth after spontaneous onset of labour (excluding elective caesarean section and induction of labour). This method was repeated for the selected population of women at low risk. Preterm birth rates among the overall population of women; preterm birth among all women with a spontaneous onset of labour; and preterm birth in a selected population of women who were either primiparous or multiparous, non-Indigenous; aged 20-40 years and who gave birth to a live singleton baby after the spontaneous onset of labour. Over the 10-year study period, the proportion of all women having a live preterm birth in Australia increased by 12.1% (from 5.9% in 1994 to 6.6% in 2003). Among women with a spontaneous onset of labour, there was an increase of 18.3% (from 5.7 to 6.7%). Among the selected population of low-risk women after the spontaneous onset of labour, the rate increased by 10.7% (from 5.6 to 6.2%) among first time mothers and by 19.2% (4.4-5.2%) among selected multiparous women. Over the 10-year period of 1994-03, the rate of spontaneous preterm birth among low-risk women having a live singleton birth has risen in Australia.

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

To determine risk factors for poor birth outcome and their population attributable fractions. 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. 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. 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.

Outcomes during and after Pregnancy in Patients with Primary Hypercoagulable States.

Pregnant women with primary hypercoagulable states have an increased risk of recurrent fetal loss, fetal growth retardation, preclampsia, and placental abruption, as well as thromboembolism in both the antepartum and postpartum periods. Conditions that have been associated with adverse pregnancy outcomes include inherited gene mutation disorders such as Factor V Leiden G1691A (FVL); prothrombin gene mutation G20210A (PGM); hyperhomocysteinemia with C677T mutation (MTHFR); deficiencies of protein S (PS), protein C (PC), antithrombin III (ATIII); and anticardiolipin antibodies/lupus anticoagulants (LA). Screening by obstetricians for these disorders has led to an increase in diagnosis yet there are no established guidelines and therapeutic interventions are variable. A retrospective chart review was conducted on 59 women and 197 pregnancies (1–12 per pt) in whom primary hypercoagulable state was diagnosed: FVL (n=7), PGM (n=11), MTHFR (n=3), ATIII (n=2), PC (n=1), PS (n=8), LA (n=10), and those with more than one thrombophilic risk (TR) (n=12) or lupus (n=2). Of the 197 pregnancies, only 106 (54%) were carried to term in 50 pts (85%). Of the remaining 91 pregnancies, there were 16 terminations, 5 ectopic pregnancies and 4 preterm live births. 66 fetal losses occurred: 45 in the first trimester (26 with single TR/19 with >1 TR), 19 in the 2nd–3rd trimester (14 with single TR/5 with > 1 TR) and 2 unknown. See Table for risk of fetal loss by class of hypercoagulable state. Venous thromboembolism occurred in 8/106 (8%) of term pregnancies, including 5 postpartum. Of women with previous fetal losses, management with anticoagulation (A/C) subsequently was utilized in 20 pregnancies: 9 low molecular weight heparin (LMWH), 6 LMWH+aspirin (ASA), 3 heparin (H), 1 ASA, and 1 H+ASA. 18/20(90%) of these pregnancies resulted in live term births; 1 loss due to intracranial hemorrhage at 27 weeks in a patient on L+ASA. Compared to 146 pregnancies untreated with A/C, successful completion of pregnancy was significantly greater on A/C, 90% vs. 58% (p=0.006).Conclusions: Fetal losses secondary to TR occurred in both the first and late trimesters in high proportion of pregnancies in women with hypercoagulable states. Outcomes may be improved with the use of A/C therapy.Table -Risk of Fetal Loss by Class of Hypercoagulable StateLAPGMMTHFRPSFVLATIIIFVL/otherTrimester19/38 (24%)7/44 (16%)3/9 (33%)3/27 (11%)1/27 (4%)2/5 (40%)17/42 (40%)Trimester 2–35/38 (13%)1/36 (3%)0%5/16 (31%)2/27 (7%)1/5 (20%)4/44 (9%)

Neonatal Mortality and Morbidity after Aggressive Long-Term Tocolysis for Preterm Premature Rupture of the Membranes

Objective: To test the hypothesis that predischarge morbidity and mortality are not increased for infants admitted to our neonatal intensive care unit and whose mothers had tocolysis for >48 h plus antibiotics and steroids (aggressive long-term tocolysis) after preterm premature rupture of the membranes (PPROM) as compared with gestational age-matched infants born to mothers not treated for PPROM. Methods: A retrospective cohort study was conducted on live preterm births (≤36.0 weeks) admitted to the neonatal intensive care unit between January 1, 1999 and June 30, 2003, comparing singletons born to mothers with PPROM + tocolysis for >48 h (n = 137, group 1) with singletons born to all other mothers matched for group-1 gestational age at delivery (n = 628, group 2), excluding severe maternal complications such as insulin-dependent diabetes and preeclampsia in both groups. Primary outcome was the predischarge mortality and morbidity of the neonates. Results: In the group with post-PPROM tocolysis which lasted for 14.4 ± 14.0 days with a latency of 15.3 ± 15.3 days (time from PPROM to delivery) and 14.4 ± 14.0 days (time from the start of tocolysis to delivery), the predischarge mortality and morbidity was not increased compared to the non-treated group. The 1- and 10-min Apgar scores of between 1 and 7 were less frequent with tocolysis (p < 0.05), and oxygen use was less frequent (26.3 vs. 36.3%, p = 0.03) and shorter (8.7 vs. 19.6 days, p = 0.03). However, amniotic fluid infection syndrome and latency (i.e. >1 week) are the most potential predictors of the respiratory distress syndrome in addition to gestational age at delivery in pregnancies with post-PPROM tocolysis. Conclusions: Amniotic fluid infection syndrome and a latency of >1 week achieved by aggressive post-PPROM tocolysis lessens the advantages of extended gestational age and decreased predischarge neonatal morbidity. These findings may have important implications for the clinical management of PPROM.

94 Access to Obstetric and Neonatal Care for Very Preterm Deliveries in Central Italy

Introduction. The aim of the study was to analyse the access to obstetric and neonatal care for very preterm deliveries in an Italian region, as part of a European project (MOSAIC) involving ten countries.Methods. During 2003, data were collected in Lazio region on Termination of Pregnancy (TOP), Foetal Deaths (FD) and Live Births (LB). Very preterm (VP) cases included TOP and FD of gestational age 22–31 wks, LB of 22–31 wks or birth weight <=1500 gr. All the 58 units were classified by three level of care (n=34 level 1, n=12 level 2 and n=12 level 3). Data on deliveries from the entire population were derived from the regional hospital discharge database. A total of 770 VP cases were collected: 102 TOP, 113 FD and 555 LB, compared to 15188 TOP, 8901 FD and 51727 LB registered in the total population.Results. The percentage of VP cases occurred in level 3 units was respectively of 71,6% for TOP, 72.6% for FD and 87.7% for LB, compared to 52.1%, 36.9% and 42.7% observed for the total population in the same level of care. Among the 510 women who had a foetal death during labour or a live birth, 65,9% had received antenal steroids. The utilization of prenatal steroids is higher in level 3 units (71.6%) compared to level 1 and level 2 units (40 % and 18.9%). The transfer rate of very preterm LB from level 1 and 2 to level 3 units was 93.9%. Among the 487 LB cases occurred in level 3 the transfer rate to other units of the same level was 20.3% (n=97), compared to 1.4% observed within level 3 units in the total population.Conclusions the study indicates that effort to concentrate the very preterm births in level 3 units has been effective. The high transfer rate within level 3 units, mainly due to bed shortage and to surgical treatment, indicates the need for improvement of the services and the organization. An appropriate evaluation of these results will include the analysis of the services in term of morbidity and mortality outcomes.

Neonatal seizures: Have we got the treatment right?

Neonatal seizures: Have we got the treatment right?

A Protocol for the Use of Enoxaparin During Pregnancy: Results from 85 Pregnancies Including 13 Multiple Gestation Pregnancies

Many practitioners consider low-molecular-weight heparin (LMWH) an alternative to unfractionated heparin, although there are limited safety data regarding maternal and fetal outcomes in patients using an LMWH during pregnancy. A retrospective chart review was performed on 72 patients with thrombophilia exposed to the LMWH, enoxaparin, during pregnancy. Eighty-five pregnancies resulted in 93 of 99 potential live births. Eleven of 12 twin pregnancies and one triplet pregnancy were successful. One preterm live birth infant of 33 weeks' gestation did not survive. Three patients with thrombophilia spontaneously aborted. A patient receiving injectable fertility treatment had spontaneously aborted one twin at 5 weeks' gestation. One patient terminated the pregnancy after discovering the presence of Down's syndrome. The mean maximum dose required to achieve a therapeutic anti-Xa level of 0.2-0.4 IU/mL at 5 to 6 hours following administration, was 38.1 mg every 12 hours (median 35 mg, range 30-75 mg every 12 hours). The mean anti-Xa level was 0.28 IU/mL (median 0.3, range 0.05-0.8 IU/mL). A total of nine patients experienced bleeding events, two requiring discontinuation of enoxaparin for the remainder of the pregnancy. Two patients experienced injection site reactions requiring discontinuation of enoxaparin. Three patients developed preeclampsia, two placenta abruptio, and one placenta previa. No thromboembolic complications or osteoporotic fractures had occurred. Enoxaparin was safe and effective for preventing thromboembolism and adverse obstetrical complications in our patients, including 12 of 13 multiple gestation pregnancies.

Platt et al. Respond to the Two Invited Commentaries

We are delighted that our proposed alternative approach to analyzing fetal and infant mortality (1) has stirred up such vigorous and thoughtful discussion (2, 3). Our approach is based on alternative denominators (i.e., fetuses at risk), which, in our view, has a sound biologic and clinical underpinning. We explicitly model the risk of death for the fetus or infant at specific times postconception. This is a logical extension and operationalization of previous work (4–6), in which we proposed incidence-based measures of birth, growth restriction, and death (including a model of “obstetric mortality”). We like Wilcox and Weinberg’s (2) suggestion that time since conception and time since birth should be included as separate time axes in the same survival model. The hazard due to livebirth is indeed highest in the first few minutes and hours of life and declines sharply thereafter, but it differs substantially depending on gestational age. While our model does not account for this sharp rise and fall in the hazard shortly after a live preterm birth, that is certainly worth considering in future refinements and extensions. Using time since birth as a continuous covariate with a declining hazard ratio as time increases is one potential approach. However, modeling this covariate would require careful attention to the assumptions of the underlying Cox model. Wilcox and Weinberg suggest that perinatal epidemiologists have been “spoiled” by the easy availability of vital statistics data and that causal pathways should be examined much more closely. They bring up a specific example of a risk factor for which preterm delivery is on the causal path between the risk factor and mortality. However, our model requires no explicit adjustment for whether the child has been born. The effect of a factor that operates through preterm delivery is then estimated without bias. On the other hand, models that condition on gestational age (either explicitly or through birth weight) can address the causal effect of only those factors that operate independently of gestational age. We agree with Klebanoff and Schoendorf (3) that removing the crossing of perinatal mortality curves is not the primary goal of statistical modeling of fetal and infant mortality. Rather, the goal is to provide a statistically sensible model that reflects the underlying biology. The fetuses-at-risk approach makes it clear that observed births at preterm gestational ages represent different proportions of the total number of conceptions for, for example, Blacks versus Whites. To understand the biology of the crossover, it is important first to understand how the source population (conceptions) develops into the observed population of births at specific gestational ages. We thank Drs. Wilcox, Weinberg, Klebanoff, and Schoendorf for their careful and insightful comments, which have helped clarify and illustrate the complexity of appropriate measurement of risk of fetal and infant mortality. We hope that continuing discussion and research will lead to a better understanding of the determinants of birth and of death during fetal life and infancy.

Subsequent Pregnancy Experience in Patients With Molar Pregnancy and Gestational Trophoblastic Tumor

The records of the New England Trophoblastic Disease Center (NETDC) since its inception in 1965 were reviewed with the aim of investigating subsequent pregnancies in patients who had been treated for molar pregnancy and persistent gestational trophoblastic tumors. Information on both partial and complete mole was included. There have been 1278 total pregnancies recorded after treatment for complete mole at NETDC and 251 subsequent pregnancies after partial mole. The rates of live full-term and preterm birth were 69% and 7.4%, respectively, in women with a complete mole and 75% and 1.6%, respectively, for women with a partial mole. There were seven stillborn infants (0.5%) and 40 (4%) congenital anomalies reported in the women who had complete mole and one stillbirth and three (0.4%) congenital anomalies in the women with partial mole. The rates of spontaneous abortion were 18% and 16%, respectively. Among women who were treated for persistent trophoblastic disease, there were 581 subsequent pregnancies. In these women the rate of full-term live birth was 68%, preterm live birth 6%, stillbirth 1.5%, congenital anomalies 2.3%, and spontaneous abortion 17%. These data are similar to the pregnancy experience of the population at large. A review of the data from four other centers showed similar results. There were no cases of premature ovarian failure recorded among the patients in the NETDC registry. Secondary infertility was reported by 4.4% of the women. Thirty-four patients experienced a second molar pregnancy. At least 6 months of normal serum human chorionic gonadotropin levels were recorded in all cases. Fourteen were repeat complete mole and 10 were repeat partial mole. Four patients who had initially had a partial mole had a complete mole, and six who had a complete mole with the first pregnancy had a subsequent partial mole. There were 35 subsequent pregnancies among 22 women who had two previous molar pregnancies, seven of which were third molar pregnancies. There were also 20 (57%) live full-term births, three spontaneous abortions, and one stillbirth. The rate of congenital anomalies was 5%. Patients who became pregnant before completion of recommended follow-up after molar pregnancy or persistent gestational trophoblastic tumors had pregnancy experiences that were comparable with the others in this study group.