Characteristics of Patients
Baseline characteristics of study subjects are shown in Table 1. It could be observed that for both GDM and ODM groups, the mean age and body mass index (BMI) of mothers were significantly higher than the W/ODM group (P = 0.003 and 0.004 respectively). As shown, no statistical differences were observed regarding gravid and history of preterm delivery between the three groups (P > 0.05). However, the prevalence history of preterm delivery for both GDM and ODM is about (0.2/0.08=2.5 ) 2.5 times higher than W/ODM women.  

Pregnancy Outcomes
As shown in Table 2, both mean gestational age at PPROM onset and delivery in W/ODM were less than two other diabetic groups (P = 0.04). However, no significant statistical difference was found between the three groups in terms of latency period between PPROM and labor onset &/or delivery (P = 0.12).

The same results were obtained between GDM with diet control and insulin therapy Table 3. For latency hours, no considerable difference has been shown between the three groups and the average gestational age at PPROM and delivery was significantly higher in W/ODM (P =0.04).

The reasons for pregnancy termination are shown in Table 4. According to this table, the most common reasons for pregnancy termination are preterm labor (PTL) and the end of 34 weeks, which were not significantly different among the three groups (P = 0.9 and P = 0.3, respectively). However, the W/ODM group had significantly higher indicated termination cases than ODM and GDM patients (P = 0.03). For the indicated termination, fetal distress is the most common reason among others.

In this study, in terms of delivery methods, Table 4 showed that the prevalence of csarean section (C/S) and vaginal delivery (NVD) cases were not significantly different between all groups (P > 0.05). Also, no considerable difference was observed for the emergency C/S among the three groups (P = 0.17). Moreover, Table 5 demonstrated that the total C/S and NVD cases are 117 (55%) and 94 (45%), respectively. Thus, the average csarean section cases were about 1.2 times higher than vaginal delivery cases. Csarean section surgery reasons are presented in Table 6 between ODM, GDM, and W/ODM groups. The childbirth methods for GDM subgroups of diet control and insulin therapy, Table 7 are the same as Table 5. Thus, there are no significant changes for childbirth methods between the subgroups and the control group.  

Maternal Outcomes

Fetus and Neonatal Outcomes
The primarily neonatal outcomes are summarized in Table 9. Neonates from the GDM and ODM groups had a significantly higher birth weight (P < 0.001) than the control group. The average fifth Apgar was significantly higher (about 20%) in GDM than in the two other groups (P < 0.001). Need to revive newborns cases were significantly lower in GDM, as well as the ODM than W/ODM cases (P < 0.001). The umbilical cord blood gas pH was significantly lower in the ODM group than the other groups, while for BE, the ODM had the largest average amount.

Table 9 showed secondary fetus and neonatal outcomes. hypoglycemia and infant death are both statistically different between the three groups. The ODM group had significantly higher hypoglycemia cases (P < 0.001) compared to W/ODM and GDM. There was a statistically considerable difference in terms of infant death cases between GDM and two other groups, with P = 0.008. For all cases, the most common cause of infant death was preterm birth. According to Table 10, the three groups were not statistically different in terms of respiratory distress (P = 0.59) and infection (P = 0.65) as well as neonatal jaundice (P = 0.8).

The maternal and neonatal outcomes for the GDM subgroups (i.e. diet and insulin therapy) and control group are summarized in Table 11. From this table, it could be concluded that the results between the two subgroups of insulin therapy and diet control are the same as the three general groups (ODM, GDM, and W/ODM). Therefore, as also shown in ‎ Table 11 the maternal and neonatal outcomes with statistically significant differences are: mean gestational age at delivery (P = 0.04), newborn weight (P = 0.00), need to revive newborns (P = 0.00), and infant death (P = 0.01). The mean gestational age at delivery in the W/ODM group is significantly lower than diet and insulin groups. Neonates from the insulin therapy group had a significantly higher newborn weight compared to other groups. The average birth weight in the insulin group is about 530 gr and 110 gr higher than W/ODM and diet group respectively. The W/ODM group has significantly the highest need to revive and infant death cases.

Table 11. Maternal and neonatal outcomes of diet control, insulin therapy, and W/ODM groups

In the first part of this study, increased BMI and maternal age were significant in diabetic groups. For both GDM and ODM groups, the BMI was more than 30 which is considered obesity. Bouvier et al., (31) suggested that factors such as maternal age and increased BMIs, might interact with other factors (e.g. hard-working) and increase PPROM risk factors and prematurity. Nohr et al., (34) Showed that the risk of PPROM and of induced preterm birth were higher in obese females (BMI ≥ 30), about twice, than in normal-weight females, especially by the end of 34th week of gestation. In this study, as well as previous studies, the history of preterm labor (PTL) is higher (but not significant) in the GDM group (see ‎0) than in the control group, while at the same time, the mean gestational age at delivery for W/ODM is lower than diabetic groups.
In our study, the most common reasons for pregnancy termination in every group were preterm labor and reaching the end of 34 weeks of pregnancy. The latency period and the incidence of chorioamnionitis were not varied between ODM, GDM, and W/ODM groups. The only considerable difference in terms of pregnancy termination was the indicated termination in which fetal distress was the most common reason. The significant difference in indicated termination between groups may be due to the greater number of control group cases. The same results were observed for the GDM subgroups (i.e. insulin and diet control). These results demonstrate that the expectant management of PPROM until the end of 34 weeks in both diabetic groups has not increased the maternal infection and the risk of preterm labor, compared to non-diabetic gravidas. Yogev (35) showed that the rate of spontaneous preterm birth in GDM does not increase compared to patients without GDM, but achieving established glycemic control levels may reduce the rate of spontaneous preterm birth in GDM. As shown in ‎0 their results are consistent with our results, as the emergency C/S is lower for GDM compared to the control group. Sheiner et al., (36), Torres (37), and Kessous et al., (38) demonstrated that the ODM in PPROM cases has an increased risk of chorioamnionitis in parallel with the increased risk of other infections; whereas Kari et al., (25) observed no significant relationship between maternal chorioamnionitis and PPROM occurrence in the diabetic patients rather the women in the nondiabetic group. The results from our study are consistent with those obtained by Kari et al., (25) in terms of the relationship between PPROM and diabetes and the occurrence of maternal infection.
As shown, for all groups, the rate of C/S was more than NVD, but there was no considerable difference between the three groups regarding overall C/S and emergency C/S prevalence. We found that the csarean delivery for PPROM cases is 50% more common in pregnant women with GDM or ODM than nondiabetic women. Previous studies have also shown that the risk of csarean section is higher (about 30% to 35%) among diabetics than W/ODM patients (13,14,39). Diabetes alone is not an indication for C/S before 38 weeks of gestation, it becomes evident that C/S may be the preferred choice for many obstetricians due to the various maternal and fetal complications associated with diabetes (40).
The interesting point about our study is the long labor duration (active phase of labor) in W/ODM groups. The newborn weight and gestational age were both higher in GDM and ODM groups, but the labor duration was higher in the W/ODM group. Although it’s impossible to get an accurate conclusion because of the small number of NVD cases, we could approximately explain this result as follows: 1) the smaller size of neonates of W/ODM may cause lower head compression pressure on the cervix which can make the active phase of labor longer, 2) another possible reason is that because of the lower gestational age of the control group; the existing number of oxytocin receptors are less than both diabetic groups.
The results suggested, for maternal outcomes, one of the significant differences among the groups was the shorter stay duration of W/ODM mothers after delivery, which was consistent with the Kari et al., (25). ODM group has the highest hospital stay of all other groups. Also, serve preeclampsia was found significantly higher in ODM groups compared to others. Wen et al., (41) demonstrated that preeclampsia is associated with a longer postoperative length of stay during delivery hospitalizations. Thus, in our study, the mean longer hospital stay for ODM might due to the higher preeclampsia cases in this group. Another reason that could explain the longer hospital stay for ODM is the longer time needed to control the serum blood glucose after delivery and change the insulin to the oral anti-glycemic agent.
As is shown in the result part, the considerable differences in neonatal outcomes were lower birth weight, lower fifth Apgar score, higher rate of reviving neonates, and more infantile death in the W/ODM group which all could be explained by the less gestational age at delivery of this group. The rate of neonatal respiratory distress was not significantly different between the three groups. However, Kari et al., (25) reported that the gestational age at delivery, Apgar score, need to revive newborn, fetal distress, and NICU admission were not significantly different between the three groups. When we compared the mentioned neonatal outcomes between subgroups of the GDM and the W/ODM group, we reached the same results. Therefore, it seems that the only leading cause of significant differences in neonatal outcomes is the less gestational age at delivery of the W/ODM group.
Regarding neonatal infections in PPROM cases, unlike Hollingsworth et al., (42), our results indicated that there is no significant relationship between neonatal infection and PPROM occurrence in diabetic women rather the women in the control group.
In our study, the rate of neonatal hypoglycemia was considerably higher in the groups with GDM and ODM compared to the diabetes-free group. Consistent with our study, Magee et al., (43), Boriboonhirunsarn et al., (20), and Bhat et al., (24) implied that hypoglycemia is the most prevalent neonatal complication related to maternal diabetes. However, Kari et al., (25) reported in their study that the relationship between diabetes and hypoglycemia was only found in ODM rather than GDM.
The umbilical cord blood gas test results showed significantly lower pH levels with high base excess and PCO2 for neonates of the ODM group. This mixed metabolic mild acidosis could be due to chromic stress in the uterine environment of the fetal life of these cases. This chronic stress as Aalipour et al., (44) showed in their study could be due to pre-existing hyperinsulinemia and hypoglycaemia in the uterine environment because of pregestational maternal diabetes.
In the second part of this study, the influences of diet and insulin therapy on neonatal and maternal consequences of PPROM cases were studied. Previous studies highlighted the fact that insulin therapy, effective treatment regimens consisting of dietary and exercise are beneficial approaches for the wellbeing of mothers, the growing fetus, and the new-born health (29,45). However, little is known about the effects of diabetes therapy approaches on PPROM cases. It is interesting to note that our results in the second part of the study confirm the first part.

The strengths of our study are the big size of PPROM patients conducted for the first time, and about 20 different maternal and neonatal study factors. The effects of gestational/mellitus diabetes and PPROM on the occurrence of maternal/neonatal sequelae were separately compared in this study. More importantly, the effect of the different types of GDM management (i.e. insulin and diet-controlled) on PPROM maternal and neonatal consequences were studied.
Our study demonstrates that conducting PPROM protocol management on PPROM cases who have gestational or overt diabetes do nothave any further risk on maternal and neonatal consequences. Due to the retrospective nature of this study, unfortunately, the past ODM patients’ records were incomplete, and also the diabetes severity based on HbA1C and FBS average was not available, accordingly the comparison of PPROM complications was not possible. Therefore, in further prospective studies, it is necessary to compare the complications of PPROM in ODM patients with diabetes type Ι and type ΙΙ. Also, studies with larger sample sizes especially with more overt diabetic patients which could be matched in terms of baseline characteristics and the gestational age of PPROM onset must be designed to assess maternal and neonatal complications and to evaluate long-term follow-up of mothers and children. However, it seems that until then, there is no need to change the PPROM management protocol for diabetic gravidas.

 

Funding Source

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and/or with the Helsinki Declaration of 1964 and later versions. Informed consent or substitute for it was obtained from all patients for being included in the study. This study was approved by the ethical committee of Tabriz University of Medical Sciences (approval number: IR.TBZMED.REC.1400.136/ date: 2021/05/03).

 

Authors declared that they have no conflict of interest.