Dharmintra Pasupathy

Factors predisposing to perinatal death related to uterine rupture during attempted vaginal birth after caesarean section: retrospective cohort study

Abstract Objective To determine the factors associated with an increased risk of perinatal death related to uterine rupture during attempted vaginal birth after caesarean section. Design Population based retrospective cohort study. Setting Data from the linked Scottish Morbidity Record and Stillbirth and Infant Death Survey of births in Scotland, 1985-98. Participants All women with one previous caesarean delivery who gave birth to a singleton infant at term by a means other than planned repeat caesarean section (n = 35 854). Main outcome measures All intrapartum uterine rupture and uterine rupture resulting in perinatal death (that is, death of the fetus or neonate). Results The overall proportion of vaginal births was 74.2% and of uterine rupture was 0.35%. The risk of intrapartum uterine rupture was higher among women who had not previously given birth vaginally (adjusted odds ratio 2.5, 95% confidence interval 1.6 to 3.9, P < 0.001) and those whose labour was induced with prostaglandin (2.9, 2.0 to 4.3, P < 0.001). Both factors were also associated with an increased risk of perinatal death due to uterine rupture. Delivery in a hospital with < 3000 births a year did not increase the overall risk of uterine rupture (1.1, 0.8 to 1.5, P = 0.67). However, the risk of perinatal death due to uterine rupture was significantly higher in hospitals with < 3000 births a year (one per 1300 births) than in hospitals with ≥ 3000 births a year (one per 4700; 3.4, 1.0 to 14.3, P = 0.04). Conclusion Women who have not previously given birth vaginally and those whose labour is induced with prostaglandin are at increased risk of uterine rupture when attempting vaginal birth after caesarean section. The risk of consequent death of the infant is higher in units with lower annual numbers of births.

The Effect of Delaying Childbirth on Primary Cesarean Section Rates

Background The relationship between population trends in delaying childbirth and rising rates of primary cesarean delivery is unclear. The aims of the present study were (1) to characterize the association between maternal age and the outcome of labor, (2) to determine the proportion of the increase in primary cesarean rates that could be attributed to changes in maternal age distribution, and (3) to determine whether the contractility of uterine smooth muscle (myometrium) varied with maternal age. Methods and Findings We utilized nationally collected data from Scotland, from 1980 to 2005, and modeled the risk of emergency cesarean section among women delivering a liveborn infant in a cephalic presentation at term. We also studied isolated myometrial strips obtained from 62 women attending for planned cesarean delivery in Cambridge, England, from 2005 to 2007. Among 583,843 eligible nulliparous women, there was a linear increase in the log odds of cesarean delivery with advancing maternal age from 16 y upwards, and this increase was unaffected by adjustment for a range of maternal characteristics (adjusted odds ratio for a 5-y increase 1.49, 95% confidence interval [CI] 1.48–1.51). Increasing maternal age was also associated with a longer duration of labor (0.49 h longer for a 5-y increase in age, 95% CI 0.46–0.51) and an increased risk of operative vaginal birth (adjusted odds ratio for a 5-y increase 1.49, 95% CI 1.48–1.50). Over the period from 1980 to 2005, the cesarean delivery rate among nulliparous women more than doubled and the proportion of women aged 30–34 y increased 3-fold, the proportion aged 35–39 y increased 7-fold, and the proportion aged ≥40 y increased 10-fold. Modeling indicated that if the age distribution had stayed the same over the period of study, 38% of the additional cesarean deliveries would have been avoided. Similar associations were observed in multiparous women. When studied in vitro, increasing maternal age was associated with reduced spontaneous activity and increased likelihood of multiphasic spontaneous myometrial contractions. Conclusions Delaying childbirth has significantly contributed to rising rates of intrapartum primary cesarean delivery. The association between increasing maternal age and the risk of intrapartum cesarean delivery is likely to have a biological basis.

Time of birth and risk of neonatal death at term: retrospective cohort study

Objective To determine the effect of time and day of birth on the risk of neonatal death at term. Design Population based retrospective cohort study. Setting Data from the linked Scottish morbidity records, Stillbirth and Infant Death Survey, and birth certificate database of live births in Scotland, 1985-2004. Subjects Liveborn term singletons with cephalic presentation. Perinatal deaths from congenital anomalies excluded. Final sample comprised 1 039 560 live births. Main outcome measure All neonatal deaths (in the first four weeks of life) unrelated to congenital abnormality, plus a subgroup of deaths ascribed to intrapartum anoxia. Results The risk of neonatal death was 4.2 per 10 000 during the normal working week (Monday to Friday, 0900-1700) and 5.6 per 10 000 at all other times (out of hours) (unadjusted odds ratio 1.3, 95% confidence interval 1.1 to 1.6). Adjustment for maternal characteristics had no material effect. The higher rate of death out of hours was because of an increased risk of death ascribed to intrapartum anoxia (adjusted odds ratio 1.7, 1.2 to 2.3). Though exclusion of elective caesarean deliveries attenuated the association between death ascribed to anoxia and delivery out of hours, a significant association persisted (adjusted odds ratio 1.5, 1.1 to 2.0). The attributable fraction of neonatal deaths ascribed to intrapartum anoxia associated with delivery out of hours was 26% (95% confidence interval 5% to 42%). Conclusions Delivering an infant outside the normal working week was associated with an increased risk of neonatal death at term ascribed to intrapartum anoxia.

Pre-pregnancy body mass index and the risk of adverse outcome in type 1 diabetic pregnancies: a population-based cohort study.

Objective To assess the risk of perinatal complications in overweight and obese women with and without type 1 diabetes (T1DM). Design Prospective population-based cohort study. Setting This study was based on data from the Swedish Medical Birth Registry from 1998 to 2007. Participants 3457 T1DM and 764 498 non-diabetic pregnancies were included. T1DM was identified based on ICD code O24.0. Mothers were categorised according to pre-pregnancy body mass index (BMI: weight in kilograms per height in square metres) as normal weight (BMI 18.5–24.9), overweight (BMI 25–29.9) or obese (BMI ≥30). Only women with singleton pregnancies and with data on BMI were included. Primary/secondary outcomes The primary outcome was large for gestational age (LGA: birth weight >90th percentile) infants. Secondary outcomes were major malformations, pre-eclampsia (PE), preterm delivery, perinatal mortality, delivery by Caesarean section and neonatal overweight. Logistic regression analysis was performed with normal weight non-diabetic women as the reference category and also within the diabetic cohort with normal weight type 1 diabetic women as the reference. The ORs were adjusted for ethnicity, maternal age, height, parity, smoking and chronic hypertension. Results 35% of women with T1DM were overweight and 18% were obese, as compared with 26% and 11%, respectively, in non-diabetic pregnancies. The incidences of adverse outcome increased with greater BMI category. As compared with non-diabetic normal weight women, the adjusted OR for obese T1DM for LGA was 13.26 (95% CI 11.27 to 15.59), major malformations 4.11 (95% CI 2.99 to 5.65) and PE 14.19 (95% CI 11.50 to 17.50). T1DM was a significant effect modifier of the association between BMI and LGA, major malformations and PE (p<0.001). Conclusion High pre-pregnancy BMI is an important risk factor for adverse outcome in type 1 diabetic pregnancies. The combined effect of both T1DM and overweight or obesity constitutes the greatest risk. It seems prudent to strive towards normal pre-pregnancy BMI in women with T1DM.

Birth Size Distribution in 3,705 Infants Born to Mothers With Type 1 Diabetes: A population-based study

OBJECTIVE To characterize birth size distribution in infants born to mothers with type 1 diabetes. In particular, the relationship between birth weight (BW) and length (BL) was studied because it may provide information on different causal pathways of fetal macrosomia commonly seen in diabetic pregnancies. RESEARCH DESIGN AND METHODS This was a population-based cohort study of 3,705 infants of type 1 diabetic mothers (1,876 boys), with a gestational age of 28–43 weeks, born in Sweden between 1998 and 2007. BW and BL were retrieved from the Medical Birth Registry and expressed as SD scores (SDS). Ponderal index (PI) was calculated as BW in g/length in cm3. A BW >90th and a PI ≤90th percentile was defined as proportionate large-for-gestational age (LGA), whereas if both BW and PI >90th percentile, the infant was categorized as disproportionately large. Values are mean (SD). RESULTS The BW distribution for offspring of type 1 diabetic mothers was bell-shaped, significantly broader, and markedly shifted to the right (BWSDS: 1.27 [1.48]) of the reference. Of the infants born to diabetic mothers, 47% were LGA, and among them, 46% were disproportionately large compared with 35% in nondiabetic LGA infants (P < 0.001). Female offspring of type 1 diabetic mothers had significantly higher BWSDS than males (1.34 vs. 1.20, P < 0.01), and preterm infants had higher BWSDS than term infants (1.41 vs. 1.23, P < 0.01) CONCLUSIONS Fetal macrosomia in type 1 diabetic pregnancies is due to a right-shift and broadening of the entire BW distribution. The large number of disproportionate LGA infants born to type 1 diabetic mothers suggests an underlying metabolic problem. Fetal macrosomia was more pronounced in preterm and female offspring of type 1 diabetic mothers.

Study protocol. A prospective cohort study of unselected primiparous women: the pregnancy outcome prediction study

BackgroundThere have been dramatic changes in the approach to screening for aneuploidy over the last 20 years. However, the approach to screening for other complications of pregnancy such as intra-uterine growth restriction, pre-eclampsia and stillbirth remains largely unchanged. Randomised controlled trials of routine application of high tech screening methods to the general population have generally failed to show improvement in outcome. We have previously reviewed this and concluded it was due, in large part, to poor performance of screening tests. Here, we report a study design where the primary aim is to generate clinically useful methods to screen women to assess their risk of adverse pregnancy outcome.Methods/designWe report the design of a prospective cohort study of unselected primiparous women recruited at the time of their first ultrasound scan. Participation involves serial phlebotomy and obstetric ultrasound at the dating ultrasound scan (typically 10–14 weeks), 20 weeks, 28 weeks and 36 weeks gestation. In addition, maternal demographic details are obtained; maternal and paternal height are measured and maternal weight is serially measured during the pregnancy; maternal, paternal and offspring DNA are collected; and, samples of placenta and membranes are collected at birth. Data will be analysed as a prospective cohort study, a case-cohort study, and a nested case-control study.DiscussionThe study is expected to provide a resource for the identification of novel biomarkers for adverse pregnancy outcome and to evaluate the performance of biomarkers and serial ultrasonography in providing clinically useful prediction of risk.

Characterization of serotonin receptors in pregnant human myometrium.

The monoamine, 5-hydroxytryptamine (5-HT), stimulates contraction of human uterine smooth muscle (myometrium), but the receptor subtypes involved have not been characterized. We studied the effects of a range of 5-HT receptor subtype-selective agonists and antagonists in isolated strips of myometrium obtained at the time of caesarean section. The 5-HT1A receptor agonist, 8-hydroxy-2-dipropylaminotetralin, produced an increase in contractions that was highly variable, of low potency, and was not significantly inhibited by the 5-HT1A antagonist WAY100635 [[O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide]. The 5-HT2 receptor agonist, α-methyl-5-hydroxytryptamine (α-Me-5-HT), produced a strong, consistent, and concentration-dependent stimulation of contractions (pEC50 = 7.60 ± 0.10, n = 5). The 5-HT2A receptor antagonist, ketanserin [3-[2-[4-(4-fluoro benzoyl)-piperidin-1-yl]ethyl]-1H-quinazoline-2,4-dione], caused a parallel shift in the response to α-Me-5-HT, with a pKB value consistent with its known affinity for the 5-HT2A receptor (pKB = 8.47 ± 0.16, n = 5), but it had no effect on the response to oxytocin. The 5-HT2B and 5-HT2C receptor agonists, BW723C86 [(α-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine)] and Ro-60-01-75 [(S)-2-(6-chloro-5-fluoro-indol-1-yl)-1-methyl-ethylamine fumarate], produced inconsistent responses at potencies that were lower than expected for activation of their cognate receptors. The response to α-Me-5-HT was unaffected by the 5-HT2B and 5-HT2C receptor antagonists, SB204741 [(N-(1-methyl-1H-indolyl-5-yl)-N-(3-methyl-5-isothiazolyl)urea)] and RS102221 [8-[5-(2,4-dimethoxy-5-(4-trifluoromethyl phenylsulphonamido)phenyl-5-oxopentyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione]. The 5-HT1B/1D receptor agonist, sumatriptan [1-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-N-methyl-methanesulfonamide], the 5-HT4 agonist, cisapride [4-amino-5-chloro-N-[1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidyl]-2-methoxy-benzamide], and the 5-HT7 agonist, AS19 [(2S)-(+)-5-(1,3,5-trimethylpyrazol-4-yl)-2-(dimethylamino)tetralin], all had no effect on myometrial contractility. 5-HT2A receptor mRNA and immunoreactivity were identified using reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry. Specific binding of [3H]ketanserin was demonstrated. This study provides strong evidence for the expression of contractile 5-HT2A receptors in pregnant human myometrium, and this receptor is a potential target for novel uterotonic therapies.

Rates of and factors associated with delivery-related perinatal death among term infants in Scotland.

CONTEXT Rates of obstetric intervention in labor, including cesarean delivery, have increased significantly in most developed countries. It is, however, unclear if this has been paralleled by decreased rates of perinatal and neonatal death associated with complications of labor at term. OBJECTIVES To determine whether rates of perinatal death at term, either during labor or in the neonatal period, have changed in Scotland during the last 20 years and whether this was associated with a reduction in deaths ascribed to intrapartum anoxia. DESIGN, SETTING, AND PARTICIPANTS A population-based, retrospective cohort study of linked data from a registry of births (Scottish Morbidity Record 02) and a registry of perinatal deaths (Scottish Stillbirth and Infant Death Survey) between 1988 and 2007. Participants included all births of a singleton infant in a cephalic presentation at term (N = 1,012,266), excluding those with perinatal death due to congenital anomaly or antepartum stillbirth. MAIN OUTCOME MEASURE Delivery-related perinatal death, defined as intrapartum stillbirth or neonatal death unrelated to congenital abnormality. These events were also subdivided into those events ascribed to intrapartum anoxia and all other causes. The risk of death was modeled using logistic regression and analyses were adjusted for maternal age, height, parity, socioeconomic deprivation status, gestational age, birth weight percentile, fetal sex, onset of labor, and the annual number of births per hospital. RESULTS During the study period, the risk of delivery-related perinatal death decreased from 8.8 to 5.5 per 10,000 births (unadjusted change, -38%; 95% confidence interval [CI], -51% to -21%). When analyzed by the cause of death, there was a significant decrease in the risk of death ascribed to intrapartum anoxia (5.7 to 3.0 per 10,000 births; unadjusted change, -48%; 95% CI, -62% to -29%), but no significant change in the risk of death ascribed to other causes. When deaths ascribed to intrapartum anoxia were analyzed by the time of death in relation to delivery, the reduction was similar comparing intrapartum stillbirths (2.6 to 1.1 per 10,000 births; unadjusted change, -60%; 95% CI, -75% to -34%) and neonatal deaths (3.1 to 1.9 per 10,000 births; unadjusted change, -38%; 95% CI, -59% to -7%). Adjustment for maternal, fetal, and obstetric factors was without material effect. CONCLUSION Rates of intrapartum stillbirth and neonatal death at term decreased in Scotland between 1988 and 2007. This decrease was only significant for deaths ascribed to intrapartum anoxia.

Trends in socioeconomic inequalities in risk of sudden infant death syndrome, other causes of infant mortality, and stillbirth in Scotland: population based study

Objectives To compare changes in inequalities in sudden infant death syndrome with other causes of infant mortality and stillbirth in Scotland, 1985-2008. Design Retrospective cohort study. Setting Scotland 1985-2008, analysed by four epochs of six years. Participants Singleton births of infants with birth weight >500 g born at 28-43 weeks’ gestation. Main outcome measures Sudden infant death syndrome, other causes of postneonatal infant death, neonatal death, and stillbirth. Odds ratios expressed as the association across the range of seven categories of Carstairs deprivation score. Results The association between deprivation and the risk of all cause stillbirth and infant death varied between the four epochs (P=0.04). This was wholly explained by variation in the risk of sudden infant death syndrome (P<0.001 for interaction). Among women living in areas of low deprivation, there was a sharp decline in the rate of sudden infant death syndrome from 1990 to 1993. Among women living in areas of high deprivation, there was a slower decline in sudden infant death syndrome rates between 1992 and 2004. Consequently, the odds ratio for the association between socioeconomic deprivation and sudden infant death syndrome increased from 2.04 (95% confidence interval 1.53 to 2.72) in 1985-90, to 7.52 (4.62 to 12.25) in 1991-6, and 9.50 (5.46 to 16.53) in 1997-2002 but fell to 1.78 (0.87 to 3.65) in 2002-8. The interaction remained significant after adjustment for maternal characteristics. Conclusion The rate of sudden infant death syndrome declined throughout Scotland in the early 1990s. The decline had a later onset and was slower among women living in areas of high deprivation, probably because of slower uptake of recommended changes in infant sleeping position. The effect was to create a strong independent association between deprivation and sudden infant death syndrome where one did not exist before.

The characteristics and health needs of pregnant women with schizophrenia compared with bipolar disorder and affective psychoses

BackgroundMost women with psychotic disorders and bipolar disorders have children but their pregnancies are at risk of adverse psychiatric and fetal outcome. The extent of modifiable risk factors – both clinical and socio-demographic – is unclear as most studies have used administrative data or recruited from specialist tertiary referral clinics. We therefore aimed to investigate the socio-demographic and clinical characteristics of an epidemiologically representative cohort of pregnant women with affective and non-affective severe mental illness.MethodsWomen with severe mental illness were identified from a large electronic mental health case register in south London, and a data linkage with national maternity Hospital Episode Statistics identified pregnancies in 2007–2011. Data were extracted using structured fields, text searching and natural language processing applications.ResultsOf 456 pregnant women identified, 236 (51.7%) had schizophrenia and related disorders, 220 (48.3%) had affective psychosis or bipolar disorder. Women with schizophrenia and related disorders were younger, less likely to have a partner in pregnancy, more likely to be black, to smoke or misuse substances and had significantly more time in the two years before pregnancy in acute care (inpatient or intensive home treatment) compared with women with affective disorders. Both groups had high levels of domestic abuse in pregnancy (recorded in 18.9%), were from relatively deprived backgrounds and had impaired functioning measured by the Health of the Nation Outcome Scale. Women in the affective group were more likely to stop medication in the first trimester (39% versus 25%) whereas women with non-affective psychoses were more likely to switch medication.ConclusionsA significant proportion of women, particularly those with non-affective psychoses, have modifiable risk factors requiring tailored care to optimize pregnancy outcomes. Mental health professionals need to be mindful of the possibility of pregnancy in women of childbearing age and prescribe and address modifiable risk factors accordingly.