Why and how was the study carried out? Each year, around 2.6 million babies are stillborn, 15 million are born preterm (<37 weeks of gestation), and 32 million are born small for gestational age (less than tenth percentile for weight, smaller than usually expected for the relevant pregnancy stage). Being born preterm or small for gestational age can increase the chance of long-term health problems. The effect of having a stillbirth, preterm birth, or small-for-gestational-age infant in a previous pregnancy on future pregnancy health has not been summarised. We identified 3399 studies of outcomes of previous pregnancies, and 17 were summarised by our study. What were the main findings? The outcome of the previous pregnancy influenced the risk of poor outcomes in the next pregnancy. Babies born to mothers who had a previous preterm birth or small-for-gestational-age birth were more likely to be stillborn. The smaller and the more preterm the previous baby, the higher the risk of stillbirth in the following pregnancy. The risk of stillbirth in the following pregnancy was doubled if the previous baby was born both preterm and small for gestational age. Babies born to mothers who had a previous stillbirth were more likely to be preterm or small for gestational age. What are the limitations of the work? We included a small number of studies, as there are not enough studies in this area (adverse birth outcomes followed by adverse cross outcomes in the next pregnancy). We found very few studies that compared the risk of small for gestational age after preterm birth or stillbirth. Definitions of stillbirth, preterm birth categories, and small for gestational age differed across studies. We did not know the cause of stillbirth for most studies. What are the implications for patients? Women who have a history of poor pregnancy outcomes are at greater risk of poor outcomes in following pregnancies. Health providers should be aware of this risk when treating patients with a history of poor pregnancy outcomes.

BackgroundLittle information exists on timing and cause of death for small-for-gestational-age (SGA) babies in low-and-middle-income-countries (LMICs), despite evidence from high-income countries suggesting critical periods for SGA babies. This study explored the timing and cause of stillbirth and early neonatal mortality (END, <7 days) by small-for-gestational age in three provinces in South Africa. In South Africa, the largest category of perinatal deaths is unexplained stillbirth, of which up to one-quarter have intra-uterine growth restriction.MethodsSecondary analysis of the South African Perinatal Problems Identification Program (PPIP) database allowed for the analysis of gestational age at death and clinically confirmed diagnosis of stillbirth and early neonatal death (END) (>1000 g and >28 weeks) across gestation. Comparisons by province, size-for-gestational-age, gestational age groups, and maternal condition at death were performed. The provinces investigated were: Western Cape (fortnightly antenatal care visits from 32 to 38 weeks), Limpopo and Mpumalanga (no antenatal care visits between 32 to 38 weeks).ResultsThere were 528,727 births in the study period and 8111 stillbirths and 5792 early neonatal deaths. Similar timing of deaths across gestation was seen for the three provinces with the greatest proportion of deaths for SGA babies at 33–37 weeks (stillbirths 52.9 %; END 43.3 %; p < 0.05). SGA babies had a greater proportion of deaths due to hypertension (SGA22.9 %; AGA 18.6 %; LGA 18.6 %; p < 0.05) and intrauterine growth restriction (SGA 6.8 %; AGA 1.7 %; LGA 1.4 %; p < 0.05). No increase was seen in poor maternal condition for SGA babies and 54.9 % of deaths had a healthy mother. Of mothers that were healthy the greatest proportion of SGA stillbirths were due to unexplained intrauterine death (53.9 %).ConclusionThere was a peak in stillbirths for SGA babies 33–37 weeks in all provinces. Detecting SGA is further complicated as in most cases the mother is healthy. Further research into Umbiflow Doppler velocimetry use in low-risk populations is warranted and may be a viable strategy to increase current detection of SGA babies at risk of mortality in LMICs.

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ObjectiveTo examine the feasibility of applying the International Classification of Diseases-perinatal mortality (ICD-PM) coding to an existing data set in the classification of perinatal deaths.MethodsOne author, a researcher with a non-clinical public health background, applied the ICD-PM coding system to South Africa’s national perinatal mortality audit system, the Perinatal Problem Identification Program. The database for this study included all perinatal deaths (n = 26 810), defined as either stillbirths (of birth weight > 1000 g and after 28 weeks of gestation) or early neonatal deaths (age 0–7 days), that occurred between 1 October 2013 and 31 December 2016. A clinical obstetrician verified the coding.FindingsThe South African classification system does not include the timing of death; however, under the ICD-PM system, deaths could be classified as antepartum (n = 15 619; 58.2%), intrapartum (n = 3725; 14.0%) or neonatal (n = 7466; 27.8%). Further, the South African classification system linked a maternal condition to only 40.3% (10 802/26 810) of all perinatal deaths; this proportion increased to 68.9% (18 467/26 810) under the ICD-PM system.ConclusionThe main benefit of using the clinically relevant and user-friendly ICD-PM system was an enhanced understanding of the data, in terms of both timing of death and maternal conditions. We have also demonstrated that it is feasible to convert an existing perinatal mortality classification system to one which is globally comparable and can inform policy-makers internationally.

Preterm birth is associated with inflammation of the fetal membranes (chorioamnionitis). We aimed to establish how chorioamnionitis affects the contractile function and phenotype of the preterm diaphragm. Pregnant ewes received intra-amniotic injections of saline or 10 mg LPS, 2 days or 7 days before delivery at 121 days of gestation (term = 150 d). Diaphragm strips were dissected for the assessment of contractile function after terminal anesthesia. The inflammatory cytokine response, myosin heavy chain (MHC) fibers, proteolytic pathways, and intracellular molecular signaling were analyzed using quantitative PCR, ELISA, immunofluorescence staining, biochemical assays, and Western blotting. Diaphragm peak twitch force and maximal tetanic force were approximately 30% lower than control values in the 2-day and 7-day LPS groups. Activation of the NF-κB pathway, an inflammatory response, and increased proteasome activity were observed in the 2-day LPS group relative to the control or 7-day LPS group. No inflammatory response was evident after a 7-day LPS exposure. Seven-day LPS exposure markedly decreased p70S6K phosphorylation, but no effect on other signaling pathways was evident. The proportion of MHC IIa fibers was lower than that for control samples in the 7-day LPS group. MHC I fiber proportions did not differ between groups. These results demonstrate that intrauterine LPS impairs preterm diaphragmatic contractility after 2-day and 7-day exposures. Diaphragm dysfunction, resulting from 2-day LPS exposure, was associated with a transient activation of proinflammatory signaling, with subsequent increased atrophic gene expression and enhanced proteasome activity. Persistently impaired contractility for the 7-day LPS exposure was associated with the down-regulation of a key component of the protein synthetic signaling pathway and a reduction in the proportions of MHC IIa fibers.