Peter G. Pryde

Perinatal death and tocolytic magnesium sulfate

Objective To determine whether there is a significant association between perinatal mortality and exposure en route for total doses of tocolytic magnesium sulfate larger than 48 g. Methods We did a case-control study in which cases were defined as neonates or fetuses who died after being exposed to tocolytic magnesium sulfate and controls were those who survived exposure. The study included fetuses and neonates who weighed between 700 and 1249 g and whose mothers had received tocolytic magnesium sulfate at Chicago Lying-in Hospital between January 1, 1986, and March 31, 1999. We excluded women who received prophylactic magnesium sulfate for preeclampsia or preeclampsia superimposed on chronic hypertension, and fetuses or neonates with major congenital anomalies. Data were analyzed by Fisher exact test, χ2 test, Student t test, Mann–Whitney U test, multivariable logistic regression, and Cochrane–Armitage trend test. Results Controlling for birth weight or gestational age, year of delivery, receipt of betamethasone, acute maternal disease, and maternal race in a multivariable model, we found that exposure to total doses of tocolytic magnesium sulfate exceeding 48 g was significantly associated with increased perinatal mortality (adjusted odds ratio 4.7; 95% confidence interval 1.1, 20.0; P = .035). Using the Cochrane–Armitage trend test, we found that a significant dose response was present (P = .03), but one that was most consistent with a threshold effect. Conclusion Our findings support the hypothesis that high doses of tocolytic magnesium sulfate are associated with increased perinatal mortality among fetuses and neonates weighing 700–1249 g.

Special relationships between fetal inflammatory response syndrome and bronchopulmonary dysplasia in neonates

Abstract Objective: To confirm previous known relationships between Fetal Inflammatory Response Syndrome (FIRS) and neonatal bronchopulmonary dysplasia (BPD) and to present information on previously unknown special relationships between inflammatory variables and BPD. Study design: At delivery, we obtained biological specimens including umbilical cord venous blood for plasma interleukin-6 levels, as well as placental histology and bacteriology. Among other neonatal outcomes, we collected prospective information on BPD. Results: Of 141 newborns in the study, 16 had BPD; 79% of these had antecedent FIRS, 27% of those without FIRS had BPD. By multivariable regression, only very low birth weight (adjusted [adj] odds ratio [OR] 32.0, 95% Confidence Interval [CI] 5.0 to positive infinity) and FIRS (adj OR 5.7, 95% CI 1.1 to 42.3) remained significant risk factors. Escherichia coli, perhaps due to its pyogenic nature (strongly elicits inflammatory responses), may have had a special relationship with BPD. Conclusions: In our data, FIRS and neonatal BPD are highly associated. It is possible that certain pyogenic bacteria in the chorioamnion space may be implicated more often than others. Condensation: Neonates having Fetal Inflammatory Response Syndrome at delivery may later develop BPD. Pyogenic bacteria, such as Escherichia coli, may be implicated more frequently.

Antenatal risk factors associated with the development of lenticulostriate vasculopathy (LSV) in neonates.

OBJECTIVE:To determine the antenatal risk factors associated with neonatal lenticulostriate vasculopathy (LSV).STUDY DESIGN:Women in preterm labor were randomized to magnesium sulfate (MgSO4), other tocolytic, or saline control. The surviving babies underwent head ultrasounds (HUS) (weeks of life 1, 2, and 4) and periodic developmental examinations (months 4, 8, 12, and 18).RESULTS:Of 140 infants, 17.1% (24) had neonatal intraventricular hemorrhage (IVH), and 10.0% (14) had LSV (half of the latter (7 of 14) had both IVH and LSV). In a regression model in which other risk factors were controlled for, the association between antenatal exposures to tocolytic MgSO4 ≥50 g and LSV were significant (adjusted odds ratio (OR), 8.3; 95% confidence interval (CI), 1.5 to 45.0; p=0.01).CONCLUSION:Based on our data and their analyses, we infer that antenatal exposure to high-dosage, tocolytic MgSO4 may be associated with LSV.

A review of the role for magnesium sulphate in preterm labour

During the last decade, the body of medical knowledge concerning the use of pharmacological doses of magnesium sulphate (MgSO4) for preterm labour has increased substantially. Several randomised controlled trials (RCTs) have provided compelling evidence that MgSO4 is the drug of choice for maternal seizure prophylaxis in pre‐eclampsia, whether preterm or term. In contrast, a recent Cochrane systematic review of the relevant contemporary literature has found no evidence basis to support the use of MgSO4 for tocolysis in preterm labour. Furthermore, associated with high‐dosage tocolytic MgSO4, recent data indicate a possible increased risk for neonatal intraventricular haemorrhage (IVH), as well as increased total paediatric mortality. It is possible, on the other hand, that the prophylactic administration of much lower dosages of MgSO4, in selected cases of preterm labour, may have a neuroprotective effect for a small number of infants.

Prenatal diagnosis of isolated femoral bent bone skeletal dysplasia: problems in differential diagnosis and genetic counseling.

Severe localized and symmetric bowing of the femora, in the absence of other significant skeletal or nonskeletal abnormalities, is a rare prenatal ultrasound finding. A 38‐year‐old woman was referred at 19 weeks gestation and ultrasound of the fetus showed severe shortening, and marked symmetric bowing of the femora. A provisional diagnosis of kyphomelic dysplasia (KD) was made. The patient elected termination of pregnancy and post mortem assessments were most consistent with kyphomelic dysplasia. KD is bent‐bone skeletal dysplasia that, in contrast to campomelic dysplasia, involves principally the femora with relative sparing of the remainder of the skeleton. KD can be difficult to distinguish, particularly from symmetric cases of femoral hypoplasia unusual facies syndrome (FH‐UFS), and few prenatal diagnoses have been reported. Because KD is thought to an be autosomal recessive disorder, the possibility that definitive diagnosis may not be possible prenatally, and even by postmortem assessment in cases choosing to abort, is an important counseling consideration.

Assessing the neuroprotective benefits for babies of antenatal magnesium sulphate: An individual participant data meta-analysis

Background Babies born preterm are at an increased risk of dying in the first weeks of life, and those who survive have a higher rate of cerebral palsy (CP) compared with babies born at term. The aim of this individual participant data (IPD) meta-analysis (MA) was to assess the effects of antenatal magnesium sulphate, compared with no magnesium treatment, given to women at risk of preterm birth on important maternal and fetal outcomes, including survival free of CP, and whether effects differed by participant or treatment characteristics such as the reason the woman was at risk of preterm birth, why treatment was given, the gestational age at which magnesium sulphate treatment was received, or the dose and timing of the administration of magnesium sulphate. Methods and findings Trials in which women considered at risk of preterm birth (<37 weeks’ gestation) were randomised to magnesium sulphate or control treatment and where neurologic outcomes for the baby were reported were eligible for inclusion. The primary outcomes were infant death or CP and severe maternal outcome potentially related to treatment. Studies were identified based on the Cochrane Pregnancy and Childbirth search strategy using the terms [antenatal or prenatal] and [magnesium] and [preterm or premature or neuroprotection or cerebral palsy]. The date of the last search was 28 February 2017. IPD were sought from investigators with eligible trials. Risk of bias was assessed using criteria from the Cochrane Collaboration. For each prespecified outcome, IPD were analysed using a 1-stage approach. All 5 trials identified were included, with 5,493 women and 6,131 babies. Overall, there was no clear effect of magnesium sulphate treatment compared with no treatment on the primary infant composite outcome of death or CP (relative risk [RR] 0.94, 95% confidence interval (CI) 0.85 to 1.05, 6,131 babies, 5 trials, p = 0.07 for heterogeneity of treatment effect across trials). In the prespecified sensitivity analysis restricted to data from the 4 trials in which the intent of treatment was fetal neuroprotection, there was a significant reduction in the risk of death or CP with magnesium sulphate treatment compared with no treatment (RR 0.86, 95% CI 0.75 to 0.99, 4,448 babies, 4 trials), with no significant heterogeneity (p = 0.28). The number needed to treat (NNT) to benefit was 41 women/babies to prevent 1 baby from either dying or having CP. For the primary outcome of severe maternal outcome potentially related to magnesium sulphate treatment, no events were recorded from the 2 trials providing data. When the individual components of the composite infant outcome were assessed, no effect was seen for death overall (RR 1.03, 95% CI 0.91 to 1.17, 6,131 babies, 5 trials) or in the analysis of death using only data from trials with the intent of fetal neuroprotection (RR 0.95, 95% CI 0.80 to 1.13, 4,448 babies, 4 trials). For cerebral palsy in survivors, magnesium sulphate treatment had a strong protective effect in both the overall analysis (RR 0.68, 95% CI 0.54 to 0.87, 4,601 babies, 5 trials, NNT to benefit 46) and the neuroprotective intent analysis (RR 0.68, 95% CI 0.53 to 0.87, 3,988 babies, 4 trials, NNT to benefit 42). No statistically significant differences were seen for any of the other secondary outcomes. The treatment effect varied little by the reason the woman was at risk of preterm birth, the gestational age at which magnesium sulphate treatment was given, the total dose received, or whether maintenance therapy was used. A limitation of the study was that not all trials could provide the data required for the planned analyses so that combined with low event rates for some important clinical events, the power to find a difference was limited. Conclusions Antenatal magnesium sulphate given prior to preterm birth for fetal neuroprotection prevents CP and reduces the combined risk of fetal/infant death or CP. Benefit is seen regardless of the reason for preterm birth, with similar effects across a range of preterm gestational ages and different treatment regimens. Widespread adoption worldwide of this relatively inexpensive, easy-to-administer treatment would lead to important global health benefits for infants born preterm.

Association between Lenticulostriate Vasculopathy (LSV) and Neonatal Intraventricular Hemorrhage (IVH)

OBJECTIVES: To determine whether there is an unconfounded association between neonatal intraventricular hemorrhage (IVH) and lenticulostriate vasculopathy (LSV (also known as thalamostriate or mineralizing vasculopathy)).STUDY DESIGN: During the conduct of the Magnesium and Neurologic Endpoints Trial (MagNET), a randomized controlled trial involving maternal, hence fetal, exposure to antenatal magnesium sulfate in the context of preterm labor, head ultrasounds were obtained for each of the surviving neonates. Because of our previous experience in the diagnosis of LSV, when ascertaining the presence of IVH, as called for by the research protocol of our study, the presence or absence of LSV was also determined.RESULTS: We found LSV to be relatively prevalent (10% (14 of 140) among surviving babies). More importantly, it was significantly associated with the occurrence of neonatal IVH, even when controlled for possible confounding (adjusted OR 9.8, 95% confidence interval 1.3 to 73.1; p=0.03).CONCLUSION: Given the known relationships between IVH and neonatal morbidity and mortality, the finding of a statistically significant association between neonatal IVH and LSV may suggest more substantial implications for the latter than previously believed.

The Risks of Extending the Controversial Use of Tocolytic Magnesium Sulfate for the Purpose of Neuroprotection in Preterm Labor

The Risks of Extending the Controversial Use of Tocolytic Magnesium Sulfate for the Purpose of Neuroprotection in Preterm Labor

Relationships between umbilical cord arterial blood pH levels at delivery and Bayley Psychomotor Development Index scores in early childhood.

Abstract Aims: To correlate data on umbilical cord arterial blood pH (pHa) levels obtained at delivery with subsequent Bayley Psychomotor Development (PDI) scores determined on the same cohort of children at age 18 months. Methods: At delivery, we obtained umbilical cord bloods for pHa levels along with other biological parameters. Following the birth cohort prospectively, at age 18 months we did a comprehensive, blinded neurodevelopmental examination to determine a PDI score for each child. Results: Over the broad range of umbilical cord arterial blood pH levels from 7.03 to 7.52, no statistically significant correlation (Pearson correlation coefficient, −0.016, P=0.88) was found between pHa at delivery and PDI scores at age 18 months. To study our finding in greater detail, we formed a subset of the data consisting only of lower pHa levels at delivery (defined as ≤7.20) and subsequent PDI scores. In this data subset, we again found that no significant relationship existed (Pearson correlation coefficient, +0.003, P=0.99). Conclusions: Our findings are consistent with the evolving hypothesis that adverse neurological outcomes in children often have etiologies other than intrapartum fetal acidemia.

Impact of prevention of teenage pregnancy on very low and low birth weight rates (VLBWR, LBWR), and neonatal and infant mortality rates (NMR, IMR) in the United States † 532

Impact of prevention of teenage pregnancy on very low and low birth weight rates (VLBWR, LBWR), and neonatal and infant mortality rates (NMR, IMR) in the United States † 532